Factor b inhibitors for treatment of ANCA-associated vasculitis

Abstract

Described herein are methods of treating ANCA-associated vasculitis (AAV) with the Factor B inhibitor iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, or hydrate thereof.

Description

FACTOR B INHIBITORSFOR TREATMENT OF ANCA-ASSOCIATED VASCULITIS FIELDThe disclosure relates to dosing and methods of treating complement driven diseases, and in particular, ANCA-associated vasculitis (AAV) with the Factor B inhibitor iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, or hydrate thereof. BACKGROUNDGranulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are primary systemic vasculitis diseases associated with the presence of circulating autoantibodies; i.e., ANCA, which have PR3 and MPO as their main target antigens. GPA and MPA, together with eosinophilic granulomatosis with polyangiitis (EGPA) are grouped as AAV, a systemic disorder characterized by inflammation of small- to mid-sized blood vessels, endothelial injury, and tissue damage (Jennette et al. 2013). GPA and MPA share non-specific clinical features of systemic inflammation including weight loss, malaise, fatigue, arthralgia and myalgia. Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected (Kitching et al. 2020). If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset (Mukhtyar et al. 2008). EGPA, although categorized as a form of AAV, has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features, and its management is typically considered as a separate entity (Kitching et al. 2020).GPA and MPA occur most commonly in older adults and are rare in children (Kitching et al. 2020). The global pooled incidence per million person-years was 9.0 for GPA and 5.9 for MPA, and the pooled prevalence per million persons was 96.8 for GPA and 39.2 for MPA (RedondoRodriguez et al. 2022). Furthermore, GPA and MPA tend to follow a different geographical distribution (Kitching et al. 2020). First, GPA is more common in patients with European descent, while MPA is more common in patients from Eastern Asia. Second, the incidence of GPA is influenced by latitude, as the incidence is lower towards the equator.Current treatment guidelines for AAV as recommended by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) (Hellmich et al. 2023) generally include GC tapering in combination with RTX or cyclophosphamide (CYC) for induction of remission. The treatment is often followed by other drugs for continued maintenance of remission, which may include additional GC, azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), leflunomide (LEF), or repeated administration of RTX. For patients with active, severe or relapsing GPA or MPA, RTX is preferred over CYC for remission induction and over MTX or AZA for remission maintenance since RTX is considered less toxic than CYC and is associated with a lower relapse rate for maintenance. For non-severe GPA or MPA, RTX is recommended whereas MTX or MMF was considered as alternative to RTX (Hellmich et al. 2023). Additional treatment includes avacopan, a C5aR inhibitor, which has recently been considered as part of a strategy to reduce exposure to GC in GPA or MPA (Hellmich et al. 2023).These treatments, although having improved remission and decreased relapse, can carry risk of serious side effects. About 59% of deaths within the first 12 months were due to therapy-associated adverse events, mainly infections (Little et al. 2010). Chronic GC use is associated with an increased risk of infection, diabetes mellitus, osteoporosis, Cushing’s syndrome, and other debilitating side effects (Sarnes et al. 2011, Goupil et al. 2013, Charlier et al. 2009, Robson et al. 2015). Moreover, repeated courses of CYC are associated with increased risk of malignancy and infertility (Chung et al. 2021). On the other hand, with RTX treatment, even though it is considered less toxic than CYC, it may increase the incidence of hypogammaglobulinemia. This is confirmed with the observation of a higher incidence of post-RTX treatment hypogammaglobulinemia being seen in patients with AAV (45%) when compared with patients with rheumatoid arthritis (22%) and connective tissue disease (9.1%). Additionally, a higher number of infections occurred in patients with AAV than in the rheumatoid arthritis and connective tissue disease under RTX treatment (Wade and Kyttaris 2021).To reduce the risk of infection, routine prophylaxis against Pneumocystis jirovecii pneumonia with trimethoprim / sulfamethoxazole is recommended for AAV patients (Chung et al. 2021, Hellmich et al. 2023). Additionally, vaccination against influenza and pneumococcal infection is recommended for patients with autoimmune diseases receiving immunosuppressive therapy (van Assen et al. 2011, Furer et al. 2020).However, vaccination host response may be impaired, especially following RTX treatment as it has been demonstrated that rheumatoid arthritis patients undergoing RTX treatment cannot initiate full immunogenicity against pneumococcal vaccination despite a boosting strategy (Nguyen et al. 2017). The impaired vaccination host response may be more noticeable in AAV patients as RTX-induced depletion of B cells and associated decreased antibody production lasted longer in AAV patients as compared to patients with rheumatoid arthritis and connective tissue disease (Thiel et al. 2017).Overall, AAV patients experience an excess of infections, malignancies and cardiovascular events as compared to the general population, which is a combination of the systemic inflammatory process associated with vasculitis and the adverse events from treatments (King et al.2017). AAV is a rare disease with limited treatment options. Toxic doses of current standard of card (SoC), mainly corticosteroids and / or cyclophosphamide, are causing a lot of the early mortality and serious morbidity in this mostly elderly population. Cyclophosphamide is a cellular toxin associated with highly increased risk for serious infections / sepsis as well as development of cancer largely contributing to high mortality in AAV population. New onset diabetes, significant weight gain, ulceration, fractures, or cataracts development are known side effects of high-dose CS and reported in AAV studies. A significant unmet need exists for targeted therapies to improve the efficacy & safety profile of current standard of care (SoC). SUMMARYThe disclosure relates to dosing and methods of treating complement driven diseases, and in particular, ANCA-associated vasculitis (AAV), with iptacopan (Formula I, shown below) or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, or hydrate thereof. Iptacopan is also known as LNP023. In particular, the disclosure provides a method of treating ANCA-associated vasculitis (AAV) in a subject, e.g., a patient, in need thereof, the method comprising administering to the subject, e.g., patient, iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof. The disclosure also provides iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in a treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., patient. The disclosure also provides a pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof , e.g., a patient, wherein the iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. The disclosure also provides use of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof in the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., a patient, wherein iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof is administered to the subject at a dose of from about 50 mg to about 500 mg. The disclosure also provides use of in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., a patient, wherein iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. In an embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered orally. In another embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to from about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In an embodiment, each dose is administered twice daily (b.i.d.), e.g., about every 12 hours, to thereby treat the subject, e.g., patient (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In one embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered at a dose of 200 mg orally twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In one embodiment, the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).In another embodiment, provided herein is a method for maintaining the remission of AAV or preventing relapse of AAV in a subject in need thereof, e.g., patient, wherein the subject has a remission of AAV, e.g., AAV that is controlled or partially controlled, by a previous treatment. In another embodiment, provided herein is a method for maintaining the remission of AAV or preventing relapse of AAV in a subject in need thereof, e.g., patient, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof, wherein the subject has a remission of AAV , e.g., AAV that is controlled or partially controlled, resulting from a previous treatment. In another embodiment, provided herein is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, e.g., patient, wherein the subject has a remission of AAV, e.g., AAV that is controlled or partially controlled, resulting from a previous treatment. In some embodiment, the previous treatment comprises a treatment with iptacopan or a pharmaceutically acceptable salt or hydrate thereof, and / or a treatment with an immunosuppressant, e.g., a corticosteroid, and / or rituximab. In one embodiment, the dose of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof applied to the subject for maintaining the remission is from about 50 mg to about 500 mg, e.g., from about 50 mg to from about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In one embodiment, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).In one embodiment, the subject receives a dose of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In another embodiment, the subject receives two doses of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In one embodiment, the subject receives two doses per day, i.e. twice daily (b.i.d.). In some embodiments, the two doses are administered to the subject every 12 hours. The dosing amount refers to the anhydrous free base of iptacopan hydrochloride. In one embodiment, the subject receives 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In certain embodiments, the subject further receives a corticosteroid at a dose of ≤5 mg / day. In one embodiment, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA). In one embodiment, provided here is a method for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., patient, comprising: (1) administering to the subject, during an induction period, iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride); and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, e.g., cyclophosphamide, a steroid, and rituximab; and (2) administering to the subject, during a maintenance period post the induction period, iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride); wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment. In one embodiment, provided here is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., patient, comprising: (1) administering to the subject during an induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily; wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment. In certain embodiments, during the maintenance period, the subject further receives a corticosteroid at a dose of ≤5 mg / day. In one embodiment, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA). In another embodiment, provided here is a method for reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises administering to the subject iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof at a dose of from about 50 mg to about 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period. In one embodiment, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA). In an embodiment of the methods and uses provided herein, the subject has newly-diagnosed or relapsed AAV. In some embodiments, the newly-diagnosed or relapsed AAV is granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA), which requires treatment with rituximab and / or cyclophosphamide. In further embodiments, the method or use further comprises administering to the subject an immunosuppressant, a steroid, e.g., a corticosteroid, and / or antibody rituximab. In another embodiment of the methods and uses provided herein, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof. In one embodiment, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. In one embodiment, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae. In yet another embodiment, the subject has been vaccinated against Neisseria meningitidis and Streptococcus pneumoniae. In still another embodiment, the subject has been vaccinated against Haemophilus influenzae.  BRIEF DESCRIPTION OF THE DRAWINGSThe accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate exemplary embodiments of the disclosure, and, together with the general description given above and the detailed description given below, serve to explain the features of the disclosure. FIG. 1 illustrates a schema for study design in Example 1. DETAILED DESCRIPTIONIptacopan is a low molecular weight, orally administered, first-in-class, selective protease inhibitor. It binds to FB (Bb domain), and as such, selectively inhibits the AP-dependent C3 activation by blocking catalytic activity of C3 and C5 convertases and blocks the formation of AP generated membrane attack complex (MAC) formation (Schubart et al. 2019, Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc Natl Acad Sci U S A p. 7926-7931)). Iptacopan does not block classical or lectin pathway C3 convertase formation (C4b2b) but does block the amplification loop via AP. Similarly, iptacopan will not block the formation of classical / lectin membrane attack complex but will block amplification of MAC. Iptacopan reduces complement activity; however, in immunized individuals, residual classical and lectin activity is expected to preserve MAC-dependent killing of encapsulated bacteria (e.g., N. meningitidis, S. pneumoniae, H. influenzae) and thus is not expected to increase the risk of serious infections to the same extent as an inhibitor of a terminal complement component, such as C5. Systemic iptacopan may increase the risk of infection, but with appropriate vaccinations and / or antibiotic prophylaxis it has been shown to be safe (Risitano et al. 2021). The terms “iptacopan” and “LNP023” are used herein interchangeably. Iptacopan, IUPAC name: 4-((2S,4S)-(4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl))benzoic acid, belongs to the class of Factor B inhibitors of the complement pathway and acts by inhibiting or suppressing the amplification of the complement system caused by C3 activation irrespective of the initial mechanism of activation. Iptacopan hydrochloride is chemically designated as 4-((2S,4S)-(4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl))benzoic acid hydrochloride or (2S,4S)-2-(4-Carboxyphenyl)-4-ethoxy-1-[(5-methoxy-7-methyl-1H -indol-4-yl)methyl]piperidin-1-ium chloride and is of the following Formula (I):Formula I.Iptacopan hydrochloride and methods for its preparation are disclosed in International Application No. PCT / US2014 / 046515 (WO 2015 / 009616, see Example 26d), which is incorporated herein by reference in its entirety. The form of iptacopan hydrochloride used as the investigational study drug for this study (see examples below) is a monohydrate (Form HB) as shown in the formula below:(2S,4S)-2-(4-Carboxyphenyl)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-1-ium chloride―water (1 / 1) or 4-{(2S ,4S )-4-Ethoxy-1-[(5-methoxy-7-methyl-1H -indol-4-yl)methyl]piperidin-2-yl}benzoic acid―hydrogen chloride―water (1 / 1 / 1).Iptacopan hydrochloride monohydrate Form HB and methods for its preparation are disclosed in International Application No. PCT / IB2021 / 054225, published in WO 2021 / 234544, which is incorporated herein by reference in its entirety.Described herein is a method of treating ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., a patient, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof. Also described herein is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in a treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., patient. The disclosure also provides a pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof , e.g., a patient, wherein the iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. The disclosure also provides use of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof in the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., a patient, wherein iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof is administered to the subject at a dose of from about 50 mg to about 500 mg. The disclosure also provides use of in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., a patient, wherein iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD (powder X-ray diffraction) peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (9.2 ± 0.2)°, and (19.1 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, and (19.1 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (19.1 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (12.2 ± 0.2)°, (19.1 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm. In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (12.2 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (16.6 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°,and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (16.6 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (16.6 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the crystalline form of LNP023 hydrochloride (Form HB) can be characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, (24.0 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, (22.2 ± 0.2)°, (24.0 ± 0.2)°, and (24.6 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, (22.2 ± 0.2)°, (24.0 ± 0.2)°, (24.6 ± 0.2)°and (28.0 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm. In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (12.2 ± 0.2)°, (19.1 ± 0.2)°, and (24.6 ± 0.2)°, and at least one more peak selected from the group consisting of (10.0 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, (22.2 ± 0.2)°, (24.0 ± 0.2)°, and (28.0 ± 0.2)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm. In another embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of:(4.6 ± 0.1)°, (9.2 ± 0.1)°, and (19.1 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, and (19.1 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (19.1 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (12.2 ± 0.1)°, (19.1 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (12.2 ± 0.1)°, (19.1 ± 0.1)°, (21.3 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (12.2 ± 0.1)°, (12.6 ± 0.1)°, (16.6 ± 0.1)°, (19.1 ± 0.1)°, (21.3 ± 0.1)°,and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.1)°, (12.6 ± 0.1)°, (16.6 ± 0.1)°, (19.1 ± 0.1)°, (21.3 ± 0.1)°,and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.1)°, (12.6 ± 0.1)°, (16.6 ± 0.1)°, (19.1 ± 0.1)°, (21.3 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.1)°, (12.6 ± 0.1)°, (15.3 ± 0.1)°, (16.6 ± 0.1)°, (19.1 ± 0.1)°, (21.3 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°; or(4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, and (24.6 ± 0.2)°; or(4.6 ± 0.2)°, (6.8 ± 0.2)°, (9.2 ± 0.2)°, (10.0 ± 0.2)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.2)°, (16.6 ± 0.2)°, (17.2 ± 0.2)°, (19.1 ± 0.2)°, (20.7 ± 0.2)°, (21.3 ± 0.2)°, (24.0 ± 0.2)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.1)°, (12.6 ± 0.1)°, (15.3 ± 0.1)°, (16.6 ± 0.1)°, (17.2 ± 0.1)°, (19.1 ± 0.1)°, (20.7 ± 0.1)°, (21.3 ± 0.1)°, (22.2 ± 0.1)°, (24.0 ± 0.1)°, and (24.6 ± 0.1)°; or(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (10.0 ± 0.1)°, (12.2 ± 0.2)°, (12.6 ± 0.2)°, (15.3 ± 0.1)°, (16.6 ± 0.1)°, (17.2 ± 0.1)°, (19.1 ± 0.1)°, (20.7 ± 0.1)°, (21.3 ± 0.1)°, (22.2 ± 0.1)°, (24.0 ± 0.1)°, (24.6 ± 0.1)°and (28.0 ± 0.1)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm. In an embodiment, iptacopan hydrochloride monohydrate is characterized by the PXRD peaks identified at 2-Theta angles of (4(4.6 ± 0.1)°, (6.8 ± 0.1)°, (9.2 ± 0.1)°, (12.2 ± 0.1)°, (19.1 ± 0.1)°, and (24.6 ± 0.1)°, and at least one more peak selected from the group consisting of (10.0 ± 0.1)°, (12.6 ± 0.1)°, (15.3 ± 0.1)°, (16.6 ± 0.1)°, (17.2 ± 0.1)°, (20.7 ± 0.1)°, (21.3 ± 0.1)°, (22.2 ± 0.1)°, (24.0 ± 0.1)°, and (28.0 ± 0.1)°, when measured at a temperature in the range of from 20 to 30 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm.In an embodiment, iptacopan hydrochloride monohydrate is characterized by having an FTIR (Fourier transform infrared) spectrum comprising peaks at wavenumbers of (3452 ± 4) cm-1, (2875 ± 4) cm-1, (1692 ± 4) cm-1, (1439 ± 4) cm-1, and (1243 ± 4) cm-1, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.In an embodiment, iptacopan hydrochloride monohydrate is characterized by having an FTIR spectrum comprising peaks at wavenumbers of (3452± 4) cm-1, (2875 ± 4) cm-1, (1692 ± 4) cm-1, (1439 ± 4) cm-1, (1243 ± 4) cm-1 and (767± 4) cm-1, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.In an embodiment, iptacopan hydrochloride monohydrate is characterized by having an FTIR spectrum comprising peaks at wavenumbers of (3452± 4) cm-1, (2875 ± 4) cm-1, (2732 ± 4) cm-1, (1692 ± 4) cm-1, (1439 ± 4) cm-1, (1243 ± 4) cm-1, and (767± 4) cm-1, when measured at a temperature in the range of from 20 to 30 °C with a diamond ATR cell.In an embodiment, iptacopan hydrochloride monohydrate is characterized by having a DSC (differential scanning calorimetry) curve showing a broad endothermic event which ends at about 170°C, followed by exothermic decomposition at about 200°C, when measured at a heating rate of 10 K / min. In an embodiment, the broad endothermic event which ends at about 170°C, is an endothermic event in the range of 35°C to 170°C when measured at a heating rate of 10 K / min. In an embodiment, iptacopan hydrochloride monohydrate is characterized by having a TGA (thermogravimetric analysis) curve showing a mass loss at about 220°C, such as at a temperature of from 200 to 220°C, due to loss of water and residual solvents of not more than 4.5w-%, e.g., of not more than 4.3w-%, e.g., of not more than 4.0w-%, e.g., of not more than 3.8 w-%, for example of not more than 3.4w-%, based on the weight of the crystalline form, when heated from 30 to 300 °C at a rate of 20 K / min.In an embodiment, iptacopan hydrochloride monohydrate is characterized by showing a mass change of not more than 4.5w-%, e.g., of not more than 4.0 w-%, e.g., of not more than 3.0 w-%, e.g., of not more than 2.0 w-%, for example of not more than 1.8 w%, 1.6 w-%, 1.5 w-% or 1.4w-%, based on the weight of the crystalline form, when measured with DVS at a relative humidity in the range of from 0 to 95% and a temperature of (25 ± 1.0)°C. In an embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered orally. In another embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered at a dose of from about 50 mg to about 500 mg, e.g., from 50 mg to 500 mg. In one embodiment, the dose ranges from about 50 mg to about 250 mg e.g., from 50 mg to 250 mg. In another embodiment, the dose ranges from about 100 mg to about 200 mg, e.g., from 100 mg to 200 mg. In certain embodiments, the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg. In certain embodiments, the dose is 50 mg, 75 mg, 100 mg, 150 mg, or 200 mg. In an embodiment, the subject receives iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In another embodiment, the subject receives two doses of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In one embodiment, the subject receives two doses per day, i.e. twice daily (b.i.d.). In some embodiments, the two doses are administered to the subject every 12 hours. The dosing amount refers to the anhydrous free base of iptacopan hydrochloride. In one embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered to the subject at a dose of 200 mg orally twice daily.In certain embodiments, the disclosed method or use further comprises administering to the subject at least one additional therapeutic agent selected from an immunosuppressant and / or rituximab. The at least one additional therapeutic agent may comprise a non-steroidal immunosuppressant, which may be selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide. In certain embodiments, the subject is administered a corticosteroid (or glucocorticoid). In certain embodiments, the corticosteroid may be chosen from prednisone, prednisolone, triamcinolone, methylprednisolone, and dexamethasone. In some embodiment, the subject has been administered the corticosteroid prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.In certain embodiments, the subject is administered rituximab.In certain embodiments, the subject has been treated with the at least one additional therapeutic agent prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof. In certain embodiments, the at least one additional therapeutic agent is administered to the subject concurrently with the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof during an induction period. In certain embodiments, the induction period is a period of 4 to 24 weeks, e.g., 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks, after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof. In certain embodiments, during the induction period, the subject is administered: (1) about 200 mg of iptacopan or a pharmaceutically acceptable salt or hydrate thereof orally twice daily, and (2) about 1000 mg of rituximab intravenously at day 1 and week 2 from the start of the treatment, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1 from the start of the treatment. In certain embodiments, the at least one additional therapeutic agent comprises a glucocorticoid, and during the induction period, the subject is administered: (1) about 200 mg of iptacopan or a pharmaceutically acceptable salt or hydrate thereof orally twice daily, and (2) from about 40 mg / day to about 75 mg / day of the glucocorticoid, intravenously. In one embodiment, the dose of the glucocorticoid is gradually reduced to ≤5 mg / day over a period of time following the induction period, e.g., over 12 weeks to 24 weeks or over a 16-week period.In certain embodiments, the method or use further comprises that during a maintenance period post the induction period, the subject continuously receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the same dose and frequency, alone or in combination with a reduced dose of glucocorticoid. As used herein, “maintenance period” refers to a period of time following the induction period. In some embodiment, the subject receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of 200 mg twice daily during the maintenance period. In certain embodiment, during the maintenance period, the subject receives a glucocorticoid, e.g., prednisone, orally at a dose of ≤5 mg daily. In some embodiments, the subject is further treated with antibiotic prophylaxis during the maintenance period.In certain embodiments, the subject is newly diagnosed or relapsed AAV subject, e.g., patient. Relapsed AAV subjects, e.g., patient, refers to individuals who have previously been diagnosed with AAV, and who have experienced a return or worsening of symptoms after a period of improvement or remission. Relapse in these subjects indicates that the disease has become active again, requiring further medical evaluation and possibly adjustments in treatment. In certain embodiments, the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In certain embodiments, the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA). In certain embodiments, the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide. In certain embodiments, the subject is responsive to anti-PR3 or anti-MPO antibodies treatment. In certain embodiments, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. In certain embodiments, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae. In certain embodiments, the subject has a baseline level of circulating IgG of greater than 4.0 g / L.In certain embodiments, the subject is an adult.In certain embodiments, the subject has a remission of AAV, i.e., controlled or partially controlled AAV, resulting from the prior administration of the at least one additional therapeutic agent. In this situation, the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof is for maintaining the remission or prevents relapse of AAV in the subject. According to the disclosure, remission refers to a state where the symptoms of the disease, e.g., AAV, are significantly reduced or completely absent. In the phase of remission in AAV subjects, e.g., patients, the inflammatory activity caused by the autoimmune response is well-controlled or halted, often as a result of successful treatment. Remission does not necessarily mean that the disease is cured or eliminated but indicates a period where the subjects, e.g., patient, experiences a significant absence or reduction of the disease's clinical manifestations. Maintaining remission typically involves ongoing monitoring and, in many cases, continued or adjusted treatment to prevent relapse. The remission status of the subject can be evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3). The BVAS, e.g., BVASv3, is a validated instrument for the assessment of disease activity and response to treatment in AAV (Mukhtyar et al., 2009). The BVASv3 form is a list of 56 items with a numerical weight attached to each item, and with each organ system having a ceiling score. These scores reflect the proportional importance of each manifestation and each organ system. The form is divided into 9 organ-based systems, with each section including symptoms / signs that are typical of that particular organ involvement in systemic vasculitis. Completion of the form provides a numerical score by using the Glossary and Scoring for the BVASv3, with higher scores indicating more severe disease.In certain embodiments, the subject exhibits a remission at week 24 from the start of the treatment. In certain embodiments, the subject exhibits a complete remission at week 24 from the start of the treatment. In certain embodiments, the subject exhibits a complete remission at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks. In various embodiments, the subject exhibits a complete remission, e.g., a BVAS score of 0 and no use of glucocorticoids at a dose of greater than 5 mg / day, at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks. In some embodiments, the subject may exhibit a remission rate of greater than 72% at week 24 from the start of said treatment. In certain embodiments, the subject exhibits a sustained remission without major relapse until week 48, from the start of said treatment. As used herein, “major relapse” refers to occurrence of at least 1 major items of BVAS or at least 3 minor items or 1 or 2 minor items recorded at two consecutive visits after BVAS=0. As used herein, “minor relapse” refers to occurrence of 1 or 2 minor items of BVAS after BVAS=0. In certain embodiments, the subject exhibits a remission rate of greater than 65%, e.g., 65.7%, at week 48 from the start of said treatment. In certain embodiments, the subject exhibits a BVAS score of 0 within from about 80 days to about 100 days, e.g., about 90 days, after starting said treatment.In certain other embodiments, the subject exhibits an improved renal function of Estimated Glomerular Filtration Rate (eGFR). In certain other embodiments, the subject exhibits eGFR improvement of at least 5 ml / min / 1.73m2. In certain other embodiments, said eGFR improvement is exhibited over 48 weeks after starting said treatment. In certain other embodiments, the subject exhibits an improved renal function, assessed by minimal clinically important difference (MCID) of Estimated Glomerular Filtration Rate (eGFR), e.g., with eGFR improvement of at least 5 ml / min / 1.73m2, over 48 weeks after starting said treatment.In another embodiment, provided related to a method for maintaining the remission of AAV or preventing relapse of AAV in a subject in need thereof, e.g., patient, wherein the subject has a remission of AAV, e.g., AAV that is controlled or partially controlled, by a previous treatment. In another embodiment, provided herein is a method for maintaining the remission of AAV or preventing relapse of AAV in a subject in need thereof, e.g., patient, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof, wherein the subject has a remission of AAV , e.g., AAV that is controlled or partially controlled, resulting from a previous treatment. In another embodiment, provided herein is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, e.g., patient, wherein the subject has a remission of AAV, e.g., AAV that is controlled or partially controlled, resulting from a previous treatment. In some embodiment, the previous treatment comprises a treatment with iptacopan or a pharmaceutically acceptable salt or hydrate thereof, and / or a treatment with an immunosuppressant and / or rituximab. In certain embodiments, the immunosuppressant is selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide. In one embodiment, the immunosuppressant is a corticosteroid. In some embodiments, the previous treatment comprises a treatment with (1) iptacopan, and (2) a corticosteroid and / or rituximab.In various embodiments, the dose of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof applied to the subject for maintaining the remission is from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg . In certain embodiments, the dose of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof applied to the subject for maintaining the remission is from 50 mg to 500 mg, e.g., from 50 mg to 250 mg, from 100 mg to 200 mg, at a dose of 50 mg, 75 mg, 100 mg, 150 mg, or 200 mg. In one embodiment, the subject receives iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In one embodiment, the subject receives two doses of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, with no more than three doses per day. In one embodiment, the subject receives two doses per day, i.e. twice daily (b.i.d.). In some embodiments, the two doses are administered to the subject every 12 hours. The dosing amount refers to the anhydrous free base of iptacopan hydrochloride. The In one embodiment, the subject receives 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof twice daily. In certain embodiments, the subject further receives a corticosteroid at a dose of ≤5 mg / day during the period of maintaining the remission of AAV. In certain embodiments, the remission is maintained for at least 4 weeks. In one embodiment, the remission is maintained for at least 14 weeks. In one embodiment, the remission is maintained for at least 24 weeks. In certain embodiments, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).In another embodiment, provided here is a method for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, comprising: (1) administering to the subject, during an induction period, iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride); and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, e.g., cyclophosphamide, a steroid, and rituximab; and (2) administering to the subject, during a maintenance period post the induction period, iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride); wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment. In one embodiment, provided here is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, e.g., patient, comprising: (1) administering to the subject during an induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily; wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment. In certain embodiments, the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the dosage of the steroid, non-steroidal immunosuppressant, and / or rituximab is gradually reduced or eliminated over a course from 12 weeks to 24 weeks, or about 16 weeks during the maintenance period. In some embodiments, the induction dose and the maintenance dose comprise the same amount of iptacopan or the pharmaceutically acceptable salt or hydrate thereof. In one embodiment, the induction dose and the maintenance dose comprise 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), each administered orally twice daily. In one embodiment, the dosage of the non-steroidal immunosuppressant, e.g., cyclophosphamide, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period. In certain embodiments, during the induction treatment period, the subject receives 200 mg of iptacopan orally twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), and 1000 mg of rituximab intravenously at day 1 and week 2, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1. In one embodiment, during the induction treatment period, the subject receives 200 mg of iptacopan orally twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), and from about 40 mg / day to about 75 mg / day of a steroid, e.g., prednisone, intravenously. In certain embodiments, during the maintenance period, the subject further receives a corticosteroid at a dose of ≤5 mg / day. In certain embodiments, the dosage of the non-steroidal immunosuppressant, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period. In some embodiments, the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA). In one embodiment the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).In another embodiment, provided here is a method for reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of from about 50 mg to about 500 mg twice daily, e.g., from 50 mg to 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period. In one embodiment, provided here is iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, e.g., iptacopan hydrochloride monohydrate, or hydrate thereof for use in reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the use comprises administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of from about 50 mg to about 500 mg twice daily, e.g., from 50 mg to 500 mg twice daily (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period. In one embodiment, the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated over a course of about 12 weeks to 24 weeks, or about 16 weeks.As used herein, the terms “controlled”, “partially controlled”, and “uncontrolled” describe the clinical status of patients with AAV based on the extent to which the disease symptoms and activity are managed. Controlled AAV refers to a state in which the disease symptoms are minimal or absent, indicating that the disease is well-managed. There is no significant evidence of active inflammation or organ damage, and the patient may be in remission. This disease state is achieved and maintained through appropriate treatment strategies. Partially Controlled AAV refers to a state in which the disease symptoms are somewhat managed but not completely. Patients may experience occasional or mild symptoms and flares, and some degree of inflammation or organ involvement may be present. Treatment at this stage may require adjustments to enhance disease control and prevent progression. Uncontrolled AAV refers to a state in which the disease symptoms are persistent or worsening, indicating that the disease is not well-managed. There is significant active inflammation and ongoing organ damage. Current treatments are inadequate, necessitating significant adjustments in the therapeutic approach to achieve better control over the disease.In an embodiment of the methods and uses provided herein, the subject has newly-diagnosed or relapsed AAV. In some embodiments, the newly-diagnosed or relapsed AAV is granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA), which requires treatment with rituximab and / or cyclophosphamide. In an embodiment, the subject is responsive to anti-PR3 or anti-MPO antibodies treatment. In another embodiment, the subject has a baseline level of circulating IgG of greater than 4.0 g / L. In various embodiments, the subject is an adult.In another embodiment of the methods and uses provided herein, the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof. In yet another embodiment, the subject has been vaccinated against Neisseria meningitidis and / or Streptococcus pneumoniaeand / or Haemophilus influenzae. In yet another embodiment, the subject has been vaccinated against Neisseria meningitidis. In yet another embodiment, the subject has been vaccinated against Streptococcus pneumoniae. In yet another embodiment, the subject has been vaccinated against Neisseria meningitidis and Streptococcus pneumoniae. In still another embodiment, the subject has been vaccinated against Haemophilus influenzae. In still another embodiment, the subject has been vaccinated against Neisseria meningitidis, Streptococcus pneumoniaeand Haemophilus influenzae. Also described herein are methods of selecting the target patient population, methods of monitoring treatment of the target patient population, and methods of assessing safety and efficacy of treatment of the target patient population.In another embodiment, disclosed here is iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in a treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein the treatment comprises administering to the subject iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof at a dose of from about 50 mg to about 500 mg, e.g., 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride).In another embodiment, disclosed here is iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In one embodiment, iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof may be formulated for oral administration, e.g., a capsule, which may contain 200 mg iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In yet another embodiment, disclosed here is a pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, or hydrate thereof and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject, e.g., patient, in need thereof, wherein the iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In one embodiment, the pharmaceutical composition comprises 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride).In yet another embodiment, disclosed here is use of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof in the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered to the subject at a dose of from about 50 mg to about 500 mg, e.g., 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In an embodiment, each dose is administered twice daily (b.i.d.), e.g., about every 12 hours, to thereby treat the subject, e.g., patient (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride).In yet another embodiment, disclosed here is use of in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg e.g., 200 mg (e.g., wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In an embodiment, each dose is administered twice daily (b.i.d.), e.g., about every 12 hours, to thereby treat the subject, e.g., patient (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride).The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated herein by reference in their entireties. DefinitionsUnless specific definitions are provided, the nomenclature used in connection with, and the procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Standard techniques may be used for chemical synthesis, and chemical analysis. Certain such techniques and procedures may be found for example in “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., 21st edition, 2005, which is hereby incorporated by reference for any purpose. Where permitted, all patents, applications, published applications and other publications and other data referred to throughout in the disclosure are incorporated by reference herein in their entirety.Unless otherwise indicated, the following terms have the following meanings:As used herein, “about” means within ±10% of a value.As used herein, “administering” or “administration” means providing a pharmaceutical agent to an individual, and includes, but is not limited to, administering by a medical professional and self-administering. Administration of a pharmaceutical agent to an individual can be continuous, chronic, short or intermittent. As used herein, the term “acquire” or “acquiring” as the terms are used herein, refer to obtaining possession of a physical entity (e.g.,a sample, e.g.,a blood sample or a blood plasma sample), or a value, e.g.,a numerical value, by “directly acquiring” or “indirectly acquiring” the physical entity or value. “Directly acquiring” means performing a process (e.g.,an analytical method) to obtain the physical entity or value. “Indirectly acquiring” refers to receiving the physical entity or value from another party or source (e.g.,a third-party laboratory that directly acquired the physical entity or value). Directly acquiring a value includes performing a process that includes a physical change in a sample or another substance, e.g.,performing an analytical process which includes a physical change in a substance, e.g.,a sample, performing an analytical method, e.g.,a method as described herein, e.g.,by sample analysis of bodily fluid, such as blood by, e.g.,mass spectroscopy, e.g.,LC-MS, e.g., LC-MS / MS methods.As used herein, “baseline” refers to a time prior to treatment in relation to a characteristic of a subject or a patient. As used herein, “dose” means a specified quantity of a pharmaceutical agent provided in a single administration, or in a specified time period. In certain embodiments, a dose can be administered in capsules. As used herein, the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.As used herein, “individual”, “patient”, “participant”, or “subject” means a human selected for treatment or therapy.As used herein, “pharmaceutically acceptable salts” means physiologically and pharmaceutically acceptable salts of iptacopan, i.e., salts that retain the desired biological activity of iptacopan and do not impart undesired toxicological effects thereto. The term “pharmaceutically acceptable salt” or “salt” includes a salt prepared from pharmaceutically acceptable non-toxic acids or bases, including inorganic or organic acids and bases. “Pharmaceutically acceptable salts” of iptacopan may be prepared by methods well-known in the art. For a review of pharmaceutically acceptable salts, see Stahl and Wermuth, Handbook of Pharmaceutical Salts: Properties, Selection and Use (Wiley-VCH, Weinheim, Germany, 2002). Iptacopan hydrochloride and methods for its preparation are disclosed in WO2015 / 009616 (see Example 26d), which is incorporated herein by reference in its entirety. As used herein, the term “treat” means decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a disorder or disease, e.g., AAV.Unless otherwise specified, conventional definitions of terms control and conventional stable atom valences are presumed and achieved in all formulas and groups. The articles “a” and “an” are used in this disclosure to refer to one or more than one (e.g., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.As used herein, “induction period” means a period of 4 to 24 weeks, e.g., 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks, after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.As used herein, “maintenance period” refers to a period of time following the induction period. Methods of Use or UsesIn one aspect, provided herein is a method of treating ANCA-associated vasculitis (AAV) in a subject in need thereof comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride. In an embodiment, provided herein is a method of treating ANCA-associated vasculitis (AAV) in a subject, e.g., a patient, in need thereof, the method comprising administering, e.g., orally, to the subject, e.g., patient, iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg, each dose administered twice daily (b.i.d.), e.g., about every 12 hours (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), to thereby treat the subject, e.g., patient. In one embodiment, provided here is a method of treating AAV in a subject by the use of iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, at a dose of about 200 mg twice daily.In another aspect, the disclosure provides iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, for use in the treatment of ANCA-associated vasculitis (AAV) in a subject, e.g., a patient, in need thereof. In an embodiment, the treatment comprises administering, e.g., orally, to the subject, e.g., patient, iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg, each dose to be administered twice daily (b.i.d.), e.g., about every 12 hours (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride). In another aspect, the disclosure provides use of iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject, e.g., a patient, in need thereof. In an embodiment, the treatment comprises orally administering to the subject, e.g., patient, iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg, each dose to be administered twice daily (b.i.d.), e.g., about every 12 hours (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), to thereby treat the subject, e.g., patient. In an embodiment, the subject, e.g., patient, has or is diagnosed as having newly-diagnosed or relapsed AAV. In an embodiment, the subject has or is diagnosed as having newly-diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide.In another aspect, the disclosure provides a pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject, e.g., patient, in need thereof. In an embodiment, the pharmaceutical composition is to be administered orally, at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg of iptacopan or a pharmaceutically acceptable salt or hydrate thereof, e.g., iptacopan hydrochloride, each dose to be administered twice daily (b.i.d.), e.g., about every 12 hours (wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride), to thereby treat the subject, e.g., patient.The following embodiments apply to any of the foregoing aspects provided herein and may be combined in any order. In an embodiment, the method or use comprises administering to the subject iptacopan hydrochloride. In another embodiment, the method or use comprises administering to the subject iptacopan hydrochloride monohydrate Form HB.In yet another embodiment, the method or use comprises administering to the subject iptacopan at a dose of from about 50 mg to about 500 mg, e.g., from about 50 mg to about 250 mg, from about 100 mg to about 200 mg, each administered twice daily (b.i.d.).In still another embodiment, the method or use comprises administering to the subject iptacopan at a dose of about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg, each administered twice daily (b.i.d.). In an embodiment, the dose is about 50 mg twice daily. In another embodiment, the dose is about 100 mg twice daily. In yet another embodiment, the dose is about 200 mg twice daily. In still another embodiment, iptacopan or a pharmaceutically acceptable salt or hydrate thereof is administered orally.In another embodiment, the method or use further comprises administering to the subject an immunosuppressant. In yet another embodiment, the immunosuppressant is mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide. In an embodiment, the method or use further comprises administering to the subject a corticosteroid. In an embodiment, the subject, e.g., patient, has been vaccinated prior to treatment with iptacopan or a pharmaceutically acceptable salt thereof, e.g., iptacopan hydrochloride, prior to administering iptacopan or a pharmaceutically acceptable salt thereof.In an embodiment, the subject, e.g., patient, has been vaccinated against Neisseria meningitidis (types A, C, Y and W-135) prior to administering iptacopan or a pharmaceutically acceptable salt thereof.In an embodiment, the subject, e.g., patient, has been vaccinated against Streptococcus pneumoniae (Pneumovax-23) prior to administering iptacopan or a pharmaceutically acceptable salt thereof.In an embodiment, the subject, e.g., patient, has been vaccinated against Haemophilus influenzae prior to administering iptacopan or a pharmaceutically acceptable salt thereof. SPECIFIC EMBODIMENTSWhile various specific embodiments are illustrated and described, it will be appreciated that various changes can be made without departing from the spirit and scope of the disclosure(s). The present disclosure is exemplified by the numbered embodiments set forth below.Embodiment 1. A method of treating ANCA-associated vasculitis (AAV) in a subject in need thereof comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of from about 50 mg to about 500 mg.Embodiment 2. The method of embodiment 1, wherein the method comprises administering to the subject iptacopan hydrochloride.Embodiment 3. The method of embodiment 1, wherein the method comprises administering to the subject iptacopan hydrochloride monohydrate.Embodiment 4. The method of any one of embodiments 1 to 3, wherein the dose is from about 50 mg to about 250 mg.Embodiment 5. The method of any one of embodiments 1 to 4, wherein the dose is from about 100 mg to about 200 mg.Embodiment 6. The method of any one of embodiments 1 to 5, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.Embodiment 7. The method of any one of embodiments 1 to 6, wherein the dose is about 50 mg.Embodiment 8. The method of any one of embodiments 1 to 6, wherein the dose is about 100 mg.Embodiment 9. The method of any one of embodiments 1 to 6, wherein the dose is about 200 mg.Embodiment 10. The method of any one of the preceding embodiments, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 11. The method of any one of embodiments 1 to 10, wherein each dose is administered to the subject twice daily. Embodiment 12. The method of any one of embodiments 1 to 11, wherein iptacopan or a pharmaceutically acceptable salt or hydrate thereof is administered orally.Embodiment 13. The method of any one of embodiments 1 to 12, wherein the method further comprises administering to the subject at least one additional therapeutic agent selected from an immunosuppressant and / or rituximab. Embodiment 14. The method of embodiment 13, wherein the at least one additional therapeutic agent comprises a non-steroidal immunosuppressant selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.Embodiment 15. The method of embodiment 13, wherein the subject is administered a corticosteroid (or glucocorticoid).Embodiment 16. The method of embodiment 15, wherein the corticosteroid is prednisone, prednisolone, triamcinolone, methylprednisolone, and / or dexamethasone.Embodiment 17. The method of any one of embodiments 13 to 16, wherein the subject is administered rituximab. Embodiment 18. The method of any one of the preceding embodiments, wherein the subject has been treated with at least one additional therapeutic agent prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 19. The method of embodiment 18, wherein the subject has received corticosteroid therapy prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 20. The method of any one of embodiments 18 to19, wherein the subject has a remission of AAV resulting from the prior administration of the at least one additional therapeutic agent, and wherein the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof maintains the remission or prevents relapse of AAV in the subject.Embodiment 21. The method of embodiment 20, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).Embodiment 22. The method of any one of embodiments 13 to 21, wherein the at least one additional therapeutic agent is administered to the subject concurrently with the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof during an induction period.Embodiment 23. The method of embodiment 22, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 24. The method of embodiment 22 or 23, wherein the at least one additional therapeutic agent comprises rituximab, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and(2) about 1000 mg of rituximab intravenously at day 1 and week 2 from the start of the treatment, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1 from the start of the treatment.Embodiment 25. The method of embodiment 22 or 23, wherein the at least one additional therapeutic agent comprises a glucocorticoid, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and(2) from about 40 mg / day to about 75 mg / day of the glucocorticoid, intravenously. Embodiment 26. The method of embodiment 25, wherein the dose of the glucocorticoid is gradually reduced to ≤5 mg / day over a period of time following the induction period, optionally the period of time following the induction period is about 12 weeks to about 24 weeks.Embodiment 27. The method of any one of embodiments 22 to 26, wherein the method further comprises, during a maintenance period post the induction period, the subject continuously receiving iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the same dose and frequency, alone or in combination with a reduced dose of glucocorticoid. Embodiment 28. The method of embodiment 27, wherein the subject receives iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof at a dose of 200 mg twice daily during the maintenance period.Embodiment 29. The method of embodiment 27 or 28, wherein during the maintenance period, the subject receives a glucocorticoid, orally at a dose of ≤5 mg daily.Embodiment 30. The method of any one of embodiments 27 to 29, further comprising treating the subject with antibiotic prophylaxis during the maintenance period.Embodiment 31. The method of any one of the preceding embodiments, wherein the subject has newly diagnosed or relapsed AAV. Embodiment 32. The method of any one of the preceding embodiments, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA).Embodiment 33. The method of any one of the preceding embodiments, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 34. The method of any one of the preceding embodiments, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide.Embodiment 35. The method of any one of the preceding embodiments, wherein the subject is responsive to anti-PR3 or anti-MPO antibodies treatment. Embodiment 36. The method of any one of the preceding embodiments, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.Embodiment 37. The method of any one of the preceding embodiments, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae.Embodiment 38. The method of any one of the preceding embodiments, wherein the subject has a baseline level of circulating IgG of greater than 4.0 g / L.Embodiment 39. The method of any one of the preceding embodiments, wherein the subject is an adult.Embodiment 40. The method of any one of the preceding embodiments, wherein the subject exhibits a remission at week 24 from the start of the treatment. Embodiment 41. The method of embodiment 40, wherein the subject exhibits a complete remission at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks. Embodiment 42. The method of embodiment 40 or 41, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).Embodiment 43. The method of embodiment 41 or 42, wherein the complete remission is when the subject has a BVAS, e.g., BVASv3, score of 0 and no use of glucocorticoids at a dose of greater than 5 mg / day, at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.Embodiment 44. The method of any one of embodiments 40 to 43, wherein the subject exhibits a sustained remission without major relapse until week 48, from the start of said treatment.Embodiment 45. The method of any one of embodiments 40 to 44, wherein the subject exhibits a remission rate of greater than 72% at week 24 from the start of said treatment. Embodiment 46. The method of any one of embodiments 40 to 44, wherein the subject exhibits a remission rate of greater than 65% at week 48 from the start of said treatment. Embodiment 47. The method of any one of the preceding embodiments, wherein the subject exhibits a BVAS score of 0 within from about 80 days to about 100 days, after starting said treatment.Embodiment 48. The method of any one of the preceding embodiments, wherein the subject exhibits an improved renal function, assessed by minimal clinically important difference (MCID) of Estimated Glomerular Filtration Rate (eGFR) over 48 weeks after starting said treatment.Embodiment 49. A method for maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof, at dose of from about 50 mg to about 500 mg, wherein the subject has a remission of AAV resulting from a previous treatment. Embodiment 50. The method of embodiment 49, wherein the dose is from about 50 mg to about 250 mg or from about 100 mg to about 200 mg.Embodiment 51. The method of embodiment 49 or 50, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.Embodiment 52. The method of any one of embodiments 49 to 51, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 53. The method of any one of embodiments 49 to 52, where the subject receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the dose orally twice daily.Embodiment 54. The method of any one of embodiments 49 to 53, wherein the previous treatment comprises administering to the subject:1) iptacopan or a pharmaceutically acceptable salt or hydrate thereof;2) an immunosuppressant and / or rituximab; or 3) combination thereof.Embodiment 55. The method of embodiment 54, wherein the immunosuppressant is selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.Embodiment 56. The method of embodiment 54, wherein the immunosuppressant is a corticosteroid.Embodiment 57. The method of any one of embodiments 54 to 56, wherein the previous treatment comprises a treatment with (1) iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, and (2) a corticosteroid and / or rituximab.Embodiment 58. The method of any one of embodiments 49 to 57, wherein the subject receives about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily.Embodiment 59. The method of any one of embodiments 49 to 58, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day.Embodiment 60. The method of any one of embodiments 49 to 59, wherein the remission of AAV is maintained for at least 4 weeks or at least 14 weeks. Embodiment 61. The method of embodiment 60, wherein the remission of AAV is maintained for at least 24 weeks. Embodiment 62. The method of any one of embodiments 49 to 61, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 63. A method for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, comprising:(1) administering to the subject during an induction period:iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily;wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment.Embodiment 64. The method of embodiment 63, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 65. The method of embodiment 63 or 64, wherein the induction dose and the maintenance dose comprise the same amount of iptacopan or the pharmaceutically acceptable salt or hydrate thereof.Embodiment 66. The method of any one of embodiments 63 to 65, wherein the induction dose and the maintenance dose comprises 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof, each administered orally twice daily.Embodiment 67. The method of any one of embodiments 63 to 66, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 68. The method of any of embodiments 63 to 67, wherein the dosage of the steroid, non-steroidal immunosuppressant, and / or rituximab is gradually reduced or eliminated over a course from 12 weeks to 24 weeks, or about 16 weeks during the maintenance period.Embodiment 69. The method of any one of embodiments 63 to 68, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and1000 mg of rituximab intravenously at day 1 and week 2, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1.Embodiment 70. The method of any one of embodiments 63 to 68, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, andfrom about 40 mg / day to about 75 mg / day of a steroid, intravenously. Embodiment 71. The method of any one of embodiments 63 to 70, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day during the maintenance period.Embodiment 72. The method of embodiment 63, wherein the dosage of the non-steroidal immunosuppressant, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period. Embodiment 73. The method of any one of embodiments 63 to 72, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 74. A method for reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises:administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose ranging from about 50 mg to about 500 mg twice daily, while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period. Embodiment 75. The method of embodiment 74, comprising administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof at a dose of about 200 mg orally twice daily during the initial treatment period and the subsequent treatment period.Embodiment 76. The method of any one of embodiments 74 to 75, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 77. The method of embodiment 74 to 76, wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated over a course of about 12 weeks to 24 weeks, or about 16 weeks.Embodiment 78. The method of any one of embodiments 74 to 77, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 79. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in a treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein the use comprises administering to the subject iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof at a dose of from about 50 mg to about 500 mg.Embodiment 80. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 79, wherein the use comprises administering to the subject iptacopan hydrochloride.Embodiment 81. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 79, wherein the use comprises administering to the subject iptacopan hydrochloride monohydrate.Embodiment 82. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 81, wherein the dose is from about 50 mg to about 250 mg.Embodiment 83. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 82, wherein the dose is from about 100 mg to about 200 mg.Embodiment 84. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 82, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.Embodiment 85. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 82, wherein the dose is about 50 mg.Embodiment 86. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 82, wherein the dose is about 100 mg.Embodiment 87. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 82, wherein the dose is about 200 mg.Embodiment 88. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 87, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 89. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 88, wherein each dose is administered to the subject twice daily. Embodiment 90. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 89, wherein iptacopan or a pharmaceutically acceptable salt or hydrate thereof is administered orally.Embodiment 91. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 90, wherein the use further comprises administering to the subject at least one additional therapeutic agent selected from an immunosuppressant and / or rituximab. Embodiment 92. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 91, wherein the at least one additional therapeutic agent comprises a non-steroidal immunosuppressant selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.Embodiment 93. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 91, wherein the subject is administered a corticosteroid (or glucocorticoid).Embodiment 94. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 93, wherein the corticosteroid is prednisone, prednisolone, triamcinolone, methylprednisolone, and / or dexamethasone.Embodiment 95. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 91 to 94, wherein the subject is administered rituximab. Embodiment 96. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 91 to 95, wherein the subject has been treated with at least one additional therapeutic agent prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 97. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 96, wherein the subject has received corticosteroid therapy prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 98. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 97, wherein the subject has a remission of AAV resulting from the prior administration of the at least one additional therapeutic agent, and wherein the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof maintains the remission or prevents relapse of AAV in the subject.Embodiment 99. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 98, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).Embodiment 100. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 91 to 99, wherein the at least one additional therapeutic agent is administered to the subject concurrently with the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof during an induction period.Embodiment 101. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 100, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 102. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 100 or 101, wherein the at least one additional therapeutic agent comprises rituximab, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and(2) about 1000 mg of rituximab intravenously at day 1 and week 2 from the start of the treatment, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1 from the start of the treatment.Embodiment 103. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 100 or 101, wherein the at least one additional therapeutic agent comprises a glucocorticoid, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and(2) from about 40 mg / day to about 75 mg / day of the glucocorticoid, intravenously. Embodiment 104. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 103, wherein the dose of the glucocorticoid is gradually reduced to ≤5 mg / day over a period of time following the induction period, optionally the period of time is about 12 weeks to about 24 weeks.Embodiment 105. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 100 to 104, wherein the use further comprises, during a maintenance period post the induction period, the subject continuously receiving iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the same dose and frequency, alone or in combination with a reduced dose of glucocorticoid. Embodiment 106. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 105, wherein the subject receives iptacopan or the pharmaceutically acceptable salt or hydrate thereof at a dose of 200 mg twice daily during the maintenance period.Embodiment 107. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 105 or 106, wherein during the maintenance period, the subject receives a glucocorticoid, orally at a dose of ≤5 mg daily.Embodiment 108. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 105 to 107, further comprising treating the subject with antibiotic prophylaxis during the maintenance period.Embodiment 109. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 108, wherein the subject has newly diagnosed or relapsed AAV. Embodiment 110. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 109, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA).Embodiment 111. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 110, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 112. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 111, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide.Embodiment 113. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 112, wherein the subject is responsive to anti-PR3 or anti-MPO antibodies treatment. Embodiment 114. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 113, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.Embodiment 115. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 114, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae.Embodiment 116. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 115, wherein the subject has a baseline level of circulating IgG of greater than 4.0 g / L.Embodiment 117. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 116, wherein the subject is an adult.Embodiment 118. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 117, wherein the subject exhibits a remission at week 24 from the start of the treatment. Embodiment 119. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 118, wherein the subject exhibits a complete remission at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks. Embodiment 120. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 118 or 119, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).Embodiment 121. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 120, wherein the complete remission is when the subject has a BVAS, e.g., BVASv3, score of 0 and no use of glucocorticoids at a dose of greater than 5 mg / day, at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.Embodiment 122. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 118 to 121, wherein the subject exhibits a sustained remission without major relapse until week 48, from the start of said treatment.Embodiment 123. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 118 to 122, wherein the subject exhibits a remission rate of greater than 72% at week 24 from the start of said treatment. Embodiment 124. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 118 to 122, wherein the subject exhibits a remission rate of greater than 65% at week 48 from the start of said treatment. Embodiment 125. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 124, wherein the subject exhibits a BVAS score of 0 within from about 80 days to about 100 days, after starting said treatment.Embodiment 126. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 79 to 125, wherein the subject exhibits an improved renal function, assessed by minimal clinically important difference (MCID) of Estimated Glomerular Filtration Rate (eGFR) over 48 weeks after starting said treatment.Embodiment 127. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof, at dose of from about 50 mg to about 500 mg, wherein the subject has a remission of AAV resulting from a previous treatment. Embodiment 128. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 127, wherein the dose is from about 50 mg to about 250 mg or from about 100 mg to about 200 mg.Embodiment 129. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 127, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.Embodiment 130. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 127 to 129, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 131. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 127 to 130, where the subject receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the dose orally twice daily.Embodiment 132. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 127 to 131, wherein the previous treatment comprises administering to the subject:1) iptacopan or a pharmaceutically acceptable salt or hydrate thereof;2) an immunosuppressant and / or rituximab; or 3) combination thereof.Embodiment 133. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 132, wherein the immunosuppressant is selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.Embodiment 134. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 132, wherein the immunosuppressant is a corticosteroid.Embodiment 135. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 132, wherein the previous treatment comprises a treatment with (1) iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, and (2) a corticosteroid and / or rituximab.Embodiment 136. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 127 to 135, wherein the subject receives about 200 mg of iptacopan orally twice daily.Embodiment 137. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 127 to 136, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day.Embodiment 138. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use any one of embodiments 127 to 137, wherein the remission of AAV is maintained for at least 4 weeks or at least 14 weeks. Embodiment 139. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use embodiment 138, wherein the remission of AAV is maintained for at least 24 weeks. Embodiment 140. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use any one of embodiments 127 to 139, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 141. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, comprising:(1) administering to the subject during an induction period:iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily;wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment.Embodiment 142. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 141, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.Embodiment 143. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 141 or 142, wherein the induction dose and the maintenance dose comprise the same amount of iptacopan or the pharmaceutically acceptable salt or hydrate thereof.Embodiment 144. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 143, wherein the induction dose and the maintenance dose comprises 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, each administered orally twice daily.Embodiment 145. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 144, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 146. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any of embodiments 141 to 145, wherein the dosage of the steroid, non-steroidal immunosuppressant, and / or rituximab is gradually reduced or eliminated over a course from 12 weeks to 24 weeks, or about 16 weeks during the maintenance period.Embodiment 147. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 146, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and1000 mg of rituximab intravenously at day 1 and week 2, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1.Embodiment 148. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 146, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, andfrom about 40 mg / day to about 75 mg / day of a steroid, intravenously. Embodiment 149. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 148, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day during the maintenance period.Embodiment 150. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 149, wherein the dosage of the non-steroidal immunosuppressant, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period. Embodiment 151. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 141 to 150, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 152. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises:administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose ranging from about 50 mg to about 500 mg twice daily, while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or a pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period. Embodiment 153. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 152, comprising administering iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of about 200 mg orally twice daily during the initial treatment period and the subsequent treatment period.Embodiment 154. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 152 to 153, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.Embodiment 155. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of embodiment 152 to 154, wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated over a course of about 12 weeks to 24 weeks, or about 16 weeks.Embodiment 156. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of embodiments 152 to 155, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).Embodiment 157. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. Embodiment 158. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for treating ANCA-associated vasculitis (AAV) in a subject in need thereof in accordance to any one of the preceding embodiments, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. Embodiment 159. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of any one of embodiments 79 or 158, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for oral administration. Embodiment 160. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of embodiment 159, wherein the iptacopan or a pharmaceutically acceptable salt thereof is contained in a capsule. Embodiment 161. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of embodiment 160, wherein the capsule comprises 200 mg of iptacopan or a pharmaceutically acceptable salt or hydrate thereof. Embodiment 162. A pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein the iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.Embodiment 163. The pharmaceutical composition of embodiment 162, which comprises 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof.Embodiment 164. The pharmaceutical composition of embodiment 162 or 163 for use in accordance with any one of the preceding embodiments.Embodiment 165. Use of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof in the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered to the subject at a dose of from about 50 mg to about 500 mg. Embodiment 166. Use of in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg. EXAMPLESThe disclosure is further illustrated by the following examples and synthesis schemes, which are not to be construed as limiting this disclosure in scope or spirit to the specific procedures herein described. It is to be understood that the examples are provided to illustrate certain embodiments and that no limitation to the scope of the disclosure is intended thereby. It is to be further understood that resort may be had to various other embodiments, modifications, and equivalents thereof which may suggest themselves to those skilled in the art without departing from the spirit of the present disclosure and / or scope of the appended claims. List of abbreviationsAAVAnti-neutrophil cytoplasmic Antibody-associated VasculitisACRAmerican College of RheumatologyAEAdverse EventAESIAdverse Events of Special InterestAISAggregate Improvement ScoreALPAlkaline PhosphataseALTAlanine AminotransferaseANCAAnti-Neutrophil Cytoplasm AntibodiesAPAlternative PathwayAPTTActivated Partial Thromboplastin TimeASTAspartate AminotransferaseAxMPAuxiliary Medicinal ProductAZAAzathioprineBID (b.i.d.)bis in die / twice a dayBMIBody Mass IndexBUNBlood Urea NitrogenBVASBirmingham Vasculitis Activity ScoreC3GComplement C3 GlomerulopathyCDCCenters for Disease Control and PreventionCKCreatine KinaseCKD-EPIChronic Kidney Disease Epidemiology CollaborationClinROClinician Reported OutcomesCOAClinical Outcome AssessmentCPClassical PathwayCRFCase Report / Record Form (paper or electronic)CROContract Research OrganizationCSRClinical study reportCTISClinical Trials Information SystemCTTClinical Trial TeamCWSCumulative Worsening ScoreCYCCyclophosphamideCYP3A4Cytochrome P450 3A4DMCData Monitoring CommitteeECGElectrocardiogramEDCElectronic Data CaptureeGFREstimated Glomerular Filtration RateEGPAEosinophilic Granulomatosis with PolyangiitisELISAEnzyme-linked immunosorbent assayEOSEnd of StudyEOTEnd of TrialEULAREuropean Alliance of Associations for RheumatologyFBFactor BFDAFood and Drug AdministrationFIHFirst in HumanFMVFirst Morning VoidGBMGlomerular Basement MembraneGCGlucocorticoidGCPGood Clinical PracticeGCSGlobal Clinical SupplyGGTGamma-glutamyl transferaseGLDHGlutamate DehydrogenaseGPAGranulomatosis with PolyangiitisGTIGlucocorticoid Toxicity IndexhHourHBcAbHepatitis B Virus Core AntibodyHBsAbHepatitis B Virus Surface AntibodyHBsAgHepatitis B virus surface antigenHBVHepatitis B VirusHCVHepatitis C VirusHDLHigh Density LipoproteinHIVHuman immunodeficiency virusIAInterim AnalysisIBInvestigator’s BrochureICFInformed Consent FormICHInternational Council for Harmonization of Technical Requirements for Pharmaceuticals for Human UseIECIndependent Ethics CommitteeIgANIgA NephropathyIMPInvestigational Medicinal ProductINInvestigator NotificationINRInternational Normalized RatioIRBInstitutional Review BoardIRTInteractive Response TechnologyIV (i.v.)IntravenousLDHlactate dehydrogenaseLDLLow Density LipoproteinLEFLeflunomideLFTLiver Function TestLLNlower limit of normalLLOQlower limit of quantificationLPLVLast Patient Last VisitMACMembrane Attack ComplexMCP-1Monocyte Chemoattractant Protein-1MDRDModification of Diet in Renal DiseaseMedDRAMedical dictionary for regulatory activitiesmgmilligram(s)mLmilliliter(s)MMFMycophenolate MofetilMPAMicroscopic PolyangiitisMPOMyeloperoxidaseMTXMethotrexateNGALNeutrophil Gelatinase-Associated LipocalinPDPharmacodynamic(s)PhGAPhysician Global AssessmentPKPharmacokinetic(s)PNHParoxysmal Nocturnal HemoglobinuriaPO (p.o.)Oral(ly)PPDPurified Protein DerivativePR3Proteinase 3PROPatient Reported OutcomesPTprothrombin timeQoLQuality of LifeQTcFQT interval corrected by Fridericia’s formulaRAPThe Report and Analysis PlanRTXRituximabSAESerious Adverse EventSAPStatistical Analysis PlanSF-36 v236-item Short Form survey version 2SoASchedule of ActivitiesSOCStandard of CareSUSARSuspected Unexpected Serious Adverse ReactionUACRUrinary Albumin:Creatinine RatioULNupper limit of normalUPCRUrinary Protein:Creatinine RatioVASVisual Analogue ScaleVDIVasculitis Damage IndexWHOWorld Health Organization Glossary of termsAdditional treatmentMedicinal products that may be used during the clinical trial as described in the protocol, but not as an investigational medicinal product (e.g. any background therapy)AssessmentA procedure used to generate data required by the studyAuxiliary medicinal product (AxMP)Medicinal product used for the needs of a clinical trial as described in the protocol, but not as an investigational medicinal product (e.g. rescue medication, challenge agents, background treatment or medicinal products used to assess end-points in the clinical trial).Concomitant therapy is not considered as AxMP.Background TherapyGenerally considered to be the current standard of care for a particular condition / disease, in addition to which study treatment is givenBiologic SamplesA biological specimen including, for example, blood (plasma, serum), saliva, tissue, urine, stool, etc. taken from a study participantCE markingA marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in European Union legislation providing for its affixing.CE marking of medical devices is required prior to lawfully placing them on the European Union market.Clinical Outcome Assessment (COA)A measure that describes or reflects how a participant feels, functions, or survivesClinical Trial TeamA group of people responsible for the planning, execution and reporting of all clinical trial activities. Examples of team members include the Study Lead, Medical Monitor, Trial Statistician etc.Coded DataPersonal Data which has been de-identified by the investigative center team by replacing personal identifiers with a code.CohortA group of individuals who share a common exposure, experience or characteristic, or a group of individuals followed-up or traced over timeControl drugA study intervention (active or placebo) used as a comparator to reduce assessment bias, preserve blinding of investigational drug, assess internal study validity, and / or evaluate comparative effects of the investigational drugDiscontinuation from studyPoint / time when the participant permanently stops receiving the study treatment and further protocol required assessments or follow-up, for any reason. No specific request is made to stop the use of their samples or data.Discontinuation from study treatmentPoint / time when the participant permanently stops receiving the study treatment for any reason (prior to the planned completion of study intervention administration, if any). Participant agrees to the other protocol required assessments including follow-up. No specific request is made to stop the use of their samples or data.DosageDose of the study treatment given to the participant in a time unit (e.g. 100 mg once a day, 75 mg twice a day)Electronic Data Capture (EDC)Electronic data capture (EDC) is the electronic acquisition of clinical study data using data collection systems, such as Web-based applications, interactive voice response systems and clinical laboratory interfaces. EDC includes the use of Electronic Case Report Forms (eCRFs) which are used to capture data transcribed from source data / documents used at the point of careEnd of the clinical trialThe end of the clinical trial is defined as the last visit of the last participant.EnrollmentPoint / time of participant entry into the study at which informed consent must be obtained. The action of enrolling one or more participantsEstimandAs defined in the ICH E9(R1) addendum, estimand is a precise description of the treatment effect reflecting the clinical question posed by the trial objective. It summarizes at a population-level what the outcomes would be in the same participants under different treatment conditions being compared. Attributes of an estimand include the population, variable (or endpoint) and treatment of interest, as well as the specification of how the remaining intercurrent events are addressed and a population-level summary for the variable.Healthy volunteerA person with no known significant health problems who volunteers to be a study participant Intercurrent eventsEvents occurring after treatment initiation that affect either the interpretation or the existence of the measurements associated with the clinical question of interest.Investigational drug / treatmentThe drug whose properties are being tested in the studyMedication numberA unique identifier on the label of medication kitsMis-randomized participantsMis-randomized participants are those who were not qualified for randomization and who did not take study treatment, but have been inadvertently randomized into the study or the participant allocated to an invalid stratification factorOff-siteDescribes trial activities that are performed at remote location by an off-site healthcare professional, such as procedures performed at the participant's home.Off-site healthcare Professional (OHP)A qualified healthcare professional, who performs certain protocol procedures for the participant in an off-site location such as a participant's home.Other treatmentTreatment that may be needed / allowed during the conduct of the study (i.e. concomitant or rescue therapy)PartA sub-division of a study used to evaluate specific objectives or contain different populations. For example, one study could contain a single dose part and a multiple dose part, or a part in participants with established disease and in those with newly-diagnosed diseaseParticipantA trial participant (can be a healthy volunteer or a patient). "Participant" terminology is used in the protocol whereas term "Subject" is used in data collectionParticipant numberA unique number assigned to each participant upon signing the informed consent. This number is the definitive, unique identifier for the participant and should be used to identify the participant throughout the study for all data collected, sample labels, etc.Patient-Reported Outcome (PRO)A measurement based on a report that comes directly from the participant about the status of a participant's health condition without amendment or interpretation of the participant's report by a clinician or anyone elsePeriodThe subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) which are described in the Protocol. Periods define the study phases and will be used in clinical trial database setup and eventually in analysisPersonal dataParticipant information collected by the Investigator that is coded and transferred for the purpose of the clinical trial. This data includes participant identifier information, study information and biological samples.RandomizationThe process of assigning trial participants to investigational drug or control / comparator drug using an element of chance to determine the assignments in order to reduce bias.Randomization numberA unique identifier assigned to each randomized participantRemoteDescribes any trial activities performed at a location that is not the investigative site.RescreeningIf a participant fails the initial screening and is considered as a Screen Failure, he / she can be invited once for a new Screening visit after medical judgment and as specified by the protocolRescue MedicationA medication used to control symptoms that are not adequately controlled on investigational and other study treatment.Screen FailureA participant who did not meet one or more criteria that were required for participation in the studySource Data / DocumentSource data refers to the initial record, document, or primary location from where data comes. The data source can be a database, a dataset, a spreadsheet or even hard-coded data, such as paper or eSourceStart of the clinical trialThe start of the clinical trial is defined as the signature of the informed consent by the first participantStudy treatmentAny drug or combination of drugs or intervention administered to the study participants as part of the required study procedures; includes investigational drug(s), control(s) or background therapyTreatment arm / groupA treatment arm / group defines the dose and regimen or the combination, and may consist of 1 or more cohorts.Treatment of interestThe treatment of interest and, as appropriate, the alternative treatment to which comparison will be made. These might be individual interventions, combinations of interventions administered concurrently, e.g. as add-on to standard of care, or might consist of an overall regimen involving a complex sequence of interventions. This is the treatment of interest used in describing the related clinical question of interest, which might or might not be the same as the study treatment.Variable (or endpoint)The variable (or endpoint) to be obtained for each participant that is required to address the clinical question. The specification of the variable might include whether the participant experiences an intercurrent event.Withdrawal of consentWithdrawal of consent from the study occurs when the participant explicitly requests to stop use of their data and / or biological samples AND no longer wishes to receive study treatment, AND does not agree to further protocol required assessments. This request should be in writing (depending on local regulations) and recorded in the source documentation.This request should be distinguished from a request to discontinue the study. Other study participant's privacy rights are described in the corresponding informed consent form. Example 1. A randomized, controlled study to evaluate LNP023 (iptacopan) in patients with active ANCA-associated vasculitis Protocol summary Purpose The aim of this study is to investigate the efficacy and safety of iptacopan, a selective, orally administered FB inhibitor in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) as the two main phenotypes in AAV patients. This study is a randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of iptacopan in combination with rituximab (RTX) and glucocorticoids (GC) tapering for the treatment of newly diagnosed or relapsed patients with active GPA and MPA vasculitis. Trial designThis study is a randomized, controlled study to evaluate the efficacy and safety of iptacopan 200 mg twice a day (BID) in combination with RTX induction therapy and defined GC tapering for the treatment of newly diagnosed or relapsed patients with active GPA or MPA. After Week 24 study visit, participants will enter the open-label maintenance period through Week 48 (followed by a 4-week safety follow up period ending with Week 52 visit as End of Study visit). Brief Summary:The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to SOC to induce and maintain remission in study participants with active GPA and MPA, when used in combination with RTX induction and defined GC tapering. The trial will also assess the impact of iptacopan on disease relapses, evolution of renal function and proteinuria, GC side effects, patients' immune status, and QoL.The study includes a Screening period of up to 2 weeks, followed by a 6-month double blind Induction period from Randomization to Week 24 and a 6-month open-label Maintenance period from Week 24 to Week 48, after which participants will enter a 4-week Safety follow-up period without study treatment. The total duration for each subject in the study, including Screening, will be up to about 54 weeks. Treatment of Interest:Treatment during Induction periodPrior to Randomization, participants may have received GC therapy.After Randomization, participants will receive either iptacopan 200 mg BID orally or matching placebo on top of the SOC; i.e., RTX and GC.After Randomization, all participants will receive either four (4) or two (2) consecutive, intravenous (IV) RTX doses as per center’s preference. Participants receiving 4 doses will be administered RTX IV at 375 mg / m2 every 7 days for 4 weeks. Participants receiving 2 doses will be administered RTX 1000 mg IV at Day 1 and subsequently at the Week 2 study visit.IV GC boluses are permitted at doses of maximum 3x 500 mg IV based on center’s preference and may have been initiated prior to Randomization.Oral (PO) GC therapy will start at Randomization with dose levels ranging from 40 mg / day to 75 mg / day, as per investigator's discretion, and will be tapered to ≤5 mg / day during a 16-week period.Note: During the 6-month Induction period, participants will receive antibiotic prophylaxis. Treatment during Maintenance periodAfter the Week 24 study visit, participants will enter the 6-month open-label Maintenance period.Participants who received iptacopan during the prior Induction period will continue with iptacopan 200 mg BID PO, while the matching placebo will be stopped in the Control arm.After the Week 24 study visit, participants in the Control arm will receive RTX at dose levels 500 – 1000 mg IV as per center’s preference. Participants receiving iptacopan will not receive RTX.Note: During the 6-month open-label Maintenance period, participants receiving iptacopan will continue to receive antibiotic prophylaxis; participants in the control group may discontinue their prophylaxis effective against S. pneumoniae, N. meningitidis, and H. influenzae as per the investigator's discretion. Treatment groups:Induction period: iptacopan 200 mg capsules or matching placebo capsulesMaintenance period: iptacopan 200 mg capsules (open label) for study participants who were under iptacopan during induction period. No further matching placebo for participants in the control arm. Key inclusion criteriaNewly diagnosed or relapsed GPA and MPA (according to the 2022 ACR / EULAR classification criteria for GPA and MPA) requiring treatment with RTX and GC as per investigator's judgement.BVAS assessment with ≥1 major item, or ≥3 minor items, or ≥2 renal items at Screening.Positive antibody test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies at Screening or with history of documented evidence of a positive antibody test.Patient willing to comply with antibiotic prophylaxis effective against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Key exclusion criteriaOther systemic disease which constitutes the primary illness, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), moderate to severe systemic lupus erythematosus, IgA vasculitis (Purpura Schönlein-Henoch), rheumatoid vasculitis, Sjögren's syndrome, anti-glomerular basement membrane (GBM) disease, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome or mixed connective tissue disease.Alveolar hemorrhage requiring invasive pulmonary ventilation support at Screening.Severe kidney disease defined as estimated glomerular filtration rate <15 mL / minute / 1.73 m2, or kidney failure defined as receiving renal replacement therapy such as hemo(dia)filtration, hemo- / peritoneal dialysis, or having received a kidney transplant.Received plasma exchange / -pheresis within 12 weeks prior to Screening. Objectives, Endpoints, and EstimandsObjectives and related endpoints Table 1 Objectives and related endpointsObjective(s)Endpoint(s)Primary objective(s)Endpoint(s) for primary objective(s)To assess the effect of iptacopan in maintaining remission at Week 48 compared to SOCSustained remission through Week 48 defined as complete remission at Week 24 without major relapse (refer to Table 2 for description) up to Week 48Secondary objective(s)Endpoint(s) for secondary objective(s)To assess the effect of iptacopan on  immune statusB cell counts and total IgG levels over 48 weeksTo assess the effect of iptacopan in inducing remission at Week 24Complete remission at week 24 defined as BVAS=0 with a GC dose ≤5 mg / day within Week 20 to 24To assess time to remission through Week 24Time to reach BVAS = 0To assess the effect of iptacopan on disease relapseTime to major relapse (refer to Table 2 for description) through Week 48To assess the effect of iptacopan on renal functionEstimated glomerular filtration rate (eGFR) using the CKD-EPI formula, urinary protein excretion and hematuria over 48 weeksTo assess the effect of iptacopan on glucocorticoid sparingThe cumulative dose of GCand glucocorticoid toxicity index over 48 weeksTo assess safety and tolerability of iptacopanSafety endpoints including (serious) adverse events, infectious complications, laboratory parameters and vital signs through Week 52To assess participants quality of life (QoL) and disease specific physician / patient reported outcomes (PRO)SF-36 v2 and physician / patient global assessments (Ph / PtGA) scores over 48 weeksExploratory objective(s)Endpoint(s) for exploratory objective(s) To explore host vaccination response.Specific antibody titers after vaccination during maintenance period (only iptacopan patients)To evaluate pharmacokinetics of iptacopanIptacopan plasma trough concentrationsTo explore impact of iptacopan on disease and pathway biomarkersPlasma, serum and urine biomarkers including (but not limited to):anti-MPO and anti-PR3 antibodiesFragment Bb, s-C5b9, C5a, C3a in plasma and / or urine, C3 in serumKidney injury markers in urine: monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), kidney Injury molecule-1 (KIM-1)Lung and vascular injury markers Protein profiling by SomaScanTo explore genetic conditions and drug related response mechanisms to better understand the disease and / or the safety and efficacy of iptacopanGenetic data (e.g. polymorphisms). Table 2 Definition of major and minor relapses DefinitionMajor relapseOccurrence of at least 1 major items of BVAS or at least 3 minor items or 1 or 2 minor items recorded at two consecutive visits after BVAS=0.Minor relapseOccurrence of 1 or 2 minor items of BVAS after BVAS=0. Primary EstimandsThe primary clinical question of interest is: Does the investigational treatment lead to comparable rates of sustained remission at Week 48 compared to the control treatment in adult patients diagnosed with GPA or MPA (newly diagnosed or relapsing).The purpose for targeting this treatment effect is to be able to assess the benefit of iptacopan in avoiding additional cycles of RTX after the induction period, as well as maintaining a GC dose below 5mg / day after the tapering.The primary estimand is described by the following attributes:Population: Patients with newly diagnosed or relapsed GPA or MPA only according to the inclusion / exclusion criteriaEndpoint: Sustained remission at Week 48 defined as complete remission at Week 24 (BVAS=0 with a GC dose ≤5 mg / day from Week 20 to 24) and no major relapse by Week 48.Treatment of interest: The randomized treatment (the investigational treatment iptacopan added to RTX and 16 weeks GC tapering during the Induction period, and iptacopan and a GC dose ≤5 mg / day during the Maintenance period; or the control treatment placebo added to RTX and 16 weeks GC tapering during the induction, RTX as per SOC, and a GC dose ≤5 mg / day during the Maintenance period)The summary measure: Difference in proportion of patients with sustained remission between treatmentsHandling of remaining intercurrent events:Discontinuation of study treatment for any reason: ignore (treatment policy strategy)Use of corticosteroids for any reason other than treatment of MPA or GPA at a dose exceeding an average of 20 mg / day of prednisolone (or equivalent) for more than 14 days, except corticosteroids used for RTX pre-dosing (hypothetical strategy - as if GC had not been administered)Any non-per protocol prescribed treatment to manage MPA or GPA (composite strategy) Secondary estimandsDescribed below in the section of Statistical Analysis Plan. Study designOverall designFIG. 1 illustrates the schema for the overall study design. This study is a randomized, participant and investigator blinded, placebo-controlled design during the Induction period and open label during the Maintenance period, to evaluate the efficacy and safety of iptacopan 200 mg BID (twice a day) in combination with RTX induction therapy and defined GC tapering for the treatment of newly diagnosed or relapsed patients with active GPA or MPA. After Week 24 study visit (end of the blinded Induction period), participants will enter the open-label Maintenance period through Week 48 (followed by a Week 52 safety follow-up assessment).The study consists of 4 periods:Each participant will undergo a Screening period of up to 2 weeks before eligible participants can be randomized and enter the 24-week Induction period, followed by a 24-week Maintenance period. At the end of the study treatment (Week 48), participants will enter into a 4-week Safety Follow-up period that concludes the trial with the End of Study visit (Week 52). The total duration for each study participant in the study, including Screening, will be up to 54 weeks. Screening periodA screening period of up to two weeks is allowed to assess participants’ eligibility for this trial. During this period, and prior to Randomization visit, participants may receive GC therapy. Induction periodApproximately 78 participants will be enrolled and randomized in a ratio of 1:1 to each treatment arm.After Randomization visit, participants will receive, blinded, either iptacopan 200 mg BID PO, or matching placebo, on top of SOC i.e., RTX and GC.After Randomization, all participants will receive either four (4) or two (2) consecutive, IV RTX doses as per center's preference. Participants receiving 4 doses will be administered RTX IV at 375 mg / m2 every 7 days for 4 weeks. Participants receiving 2 doses will be administered RTX 1000 mg IV at Day 1 and subsequently at the Week 2 study visit.IV GC boluses are permitted at doses of maximum 3x 500 mg based on center preference and may have been initiated prior to Randomization.Oral (PO) GC therapy will start at Randomization with dose levels ranging from 40 mg / day to 75 mg / day, as per investigator's discretion, and will be tapered to ≤5 mg / day during a 16-week period as per the protocol defined schedule.During the GC tapering, at Week 3, 6, 10 and 14 visits, on-site visit is optional and GC medication resupply can be performed remotely or anticipated at the immediate previous visit together with study medication resupply to cover 4 weeks. As a consequence, a site phone call to study participant will be performed at these visits to assess their status with GC intake during the tapering period using a pre-filled patient diary for GC intake and collect any other information. Maintenance periodAfter the Week 24 study visit, participants will enter the 6-month open-label Maintenance period.Study participants who did not achieve complete remission (BVAS=0) during Induction period will be considered as treatment failures. Participants with treatment failure should remain in the study and continue to receive the study treatment unless otherwise specified. Adequate rescue medication will be administered in case of lack of efficacy or relapse.Participants will be unblinded after all assessments at Week 24 have been completed. Participants who received iptacopan during the prior Induction period will continue with iptacopan 200 mg BID PO, while the matching placebo will be stopped in the Control arm.After the Week 24 study visit, participants in the Control arm will receive RTX at dose levels 500 – 1000 mg IV as per center's preference and GC of ≤5mg per day. Participants receiving iptacopan will not receive RTX.Study participants will return for onsite visits every 4 weeks from Week 24 to 32, and will then return at Week 40 and 48 visits which is the end of treatment (EoT) visit. Study ConductScreeningOnce the participant has signed the informed consent form, the participant may enter the Screening period. This up to 2-week Screening period will be used to assess participants eligibility. After signing the ICF, during this visit, inclusion and exclusion criteria will be assessed to verify the study candidate’s eligibility for enrollment into this study.If the eligibility criteria are not met, the study candidate should be considered as failed screening and should not proceed further in the study. RandomizationEligible study participants will return for the Randomization visit on Day 1.Eligibility must be confirmed prior to randomization and required screening assessments for eligibility must be completed prior to dosing on Day 1.Antibiotic prophylaxis effective against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae must be initiated at Day 1.For logistical reasons, study participants may reside nearby at a hotel or at site. However, if the participant stays overnight at site, this should not be considered as fulfilling the criteria for a serious safety event.Randomization will be stratified by GPA or MPA, disease status (newly diagnosed or relapsed AAV), and renal status with a threshold of eGFR at 45 mL / min / 1.73 m2. Treatment periodsStudy participants will be randomized to the respective treatment arms. Induction periodPrior to Randomization, participants may have received GC therapy.After Randomization, participants will receive either iptacopan 200 mg BID orally or matching placebo on top of the standard of care (SOC); i.e., RTX and GC. Participants will receive their first iptacopan (or placebo) dosing on site during the Day 1 study visit. At subsequent on-site study visits, participants will take their morning dose only after respective assessments have been performed. At on-site visits, study participants will be provided study drug (iptacopan or placebo) for self-administration at home.Throughout the Induction period, participants must comply with antibiotic prophylaxis effective against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.After Randomization, all participants will receive either four (4) or two (2) consecutive, IV RTX doses as per center's preference. Participants receiving 4 doses will be administered RTX IV at 375 mg / m2 every 7 days for 4 weeks. Participants receiving 2 doses will be administered RTX 1000 mg IV at Day 1 and subsequently at the Week 2 study visit.IV GC boluses are permitted at doses of maximum 3x 500 mg based on center preference and may have been initiated prior to Randomization.PO GC therapy will start at Randomization with dose levels ranging from 40 mg / day to 75 mg / day, as per investigator's discretion, and will be tapered to ≤5 mg / day during a 16-week period.During the GC tapering period, on-site visits on Week 3, 6, 10 and 14 are optional and GC medication resupply can be performed remotely or anticipated at the immediate previous visit together with study medication resupply to cover 4 weeks. Therefore, a site phone call to study participant will be performed at these visits to assess their status with GC intake during the tapering period using a pre-filled patient diary (by the study nurse) for GC intake and collect any other information. Maintenance periodAfter the Week 24 study visit, participants will enter the 6-month open-label Maintenance period.Participants who received iptacopan during the prior Induction period will continue with iptacopan 200 mg BID PO, while the matching placebo will be stopped in the Control arm. At on-site visits, study participants will be provided study drug (iptacopan) for self-administration at home.During the 6-month open-label Maintenance period, participants with iptacopan will continue to receive antibiotic prophylaxis; participants in the control group may discontinue their prophylaxis effective against S. pneumoniae, N. meningitidis, and H. influenzae as per the investigator's discretion.After the Week 24 study visit, participants in the Control arm will receive RTX at dose levels 500 – 1000 mg IV as per center's preference and GC of ≤ 5 mg per day. Participants receiving iptacopan will not receive RTX.Study participants will also undergo BVAS assessments as well as other scales / questionnaires, safety and PK / PD and biomarker sample collections at these study visits as indicated in the Assessment Schedule.All study visits will be ambulatory, however, for logistical reasons, it may be necessary for participants to come to the site the evening before their scheduled assessment visit. In these instances, and to accommodate the participants, they may stay overnight nearby at a hotel or at the site. However, if the participant stays overnight at site, this should not be considered as fulfilling the criteria for a serious safety event.Study participants may be contacted by the Investigator / site staff during the study to ensure compliance / monitor safety by telephone or other means, if it is deemed appropriate or necessary by the Investigator. Follow up and End of Study visit (EoS)After the last Maintenance period study visit (Week 48 EoT visit), study participants will enter a 4-week Safety Follow-up period without study drug treatment. Study participants will then be asked to return to the site at Week 52 for the EoS visit.At this visit, study participants will undergo final assessments as indicated in the Assessment schedule.Upon completion of this visit, study participants will be discharged from the study. Rationale for choice of control drugs or combination drugs and background therapyThe background treatment regimens have referred to ACR 2021, EULAR 2022 and KDIGO 2021 guidelines for treatment in patient with AAV (Chung et al. 2021, Hellmich et al. 2023, KDIGO 2021).Study participants in both treatment groups will undergo defined GC tapering starting at 40-75 mg / day in the first week and reducing to ≤5 mg / day by Week 16. Study participants will be allowed to receive ≤5 mg / day GC during the rest of the study treatment period (until Week 48). A rapid GC taper in both groups as background medication will allow the evaluation of the GC sparing effect of iptacopan compared with placebo. Study participants will be closely monitored. In case of lack of efficacy or relapse study participants will receive adequate rescue medication.IV infusions of RTX once weekly for 4 weeks starting at Day 1, or twice, on Day 1 and Week 2, as per center's preference, will be administered in combination with GC for the first 24 weeks of induction of remission. RTX has been recommended as first line therapy for induction of remission (Chung et al. 2021, Hellmich et al. 2023) and there has been an increasing preference for RTX over CYC (Springer et al. 2020). Furthermore, limiting the induction of remission treatment to RTX and GC will establish a more homogenous SOC supporting the assessment of the additional iptacopan treatment effect in participants with GPA or MPA AAV.To note, RTX treatment has been associated with increased incidence of hypogammaglobulinemia and consequently increased risk of infectious complications and compromised immune response to vaccine (Hellmich et al. 2023). The avoidance of overtreatment with RTX while maintaining remission is therefore an additional goal of this study. While participants in the control arm will receive RTX during Maintenance period as per SOC, study participants who receive iptacopan and have achieved complete remission at Week 24 will not receive RTX. Adequate rescue medication will be administered in case of lack of efficacy or relapse. The experimental (iptacopan) arm will enable a window of opportunity to perform any necessary vaccinations and to study the effect of iptacopan in preventing relapse during Maintenance period.Comparator treatment is defined as placebo during the Induction period in order to provide objective evidence of potential AE and other safety data, as well as clinical efficacy and pharmacodynamic (PD) data generated from GPA and MPA AAV participants treated with iptacopan. Placebo-controlled is justifiable since the study interventions will be added on top of existing SOC. All participants will receive RTX and IV GC induction as SOC therapy as recommended by ACR, KDIGO and EULAR guidelines (Chung et al. 2021, Hellmich et al. 2023, KDIGO 2021) for the treatment of patients with active AAV, with a standard tapering GC regimen. Purpose and timing of interim analyses / design adaptationsTwo interim analyses are planned during the study.The first interim analysis (IA1) is planned after 50% of participants (approximately 39 participants)reach Week 24. The second interim analysis (IA2) is planned after all participants recruited (approximately 78 patients) reach Week 24.At both IAs, all available data of the participants who completed Week 24, will be analyzed.Additional interim analyses may be conducted to support decision making concerning the current clinical study, the Sponsor’s clinical development projects in general, or in case of any safety concerns. End of study definitionStudy completion is defined as when the last participant finishes their last study visit and any repeated assessments associated with this visit have been documented and followed-up appropriately by the Investigator. Study populationThe study population will consist of approximately 78 male and female patients aged 18 years or older with newly diagnosed or relapsed GPA or MPA that requires treatment with RTX and GC. Inclusion CriteriaParticipants eligible for inclusion in this study must meet all of the following criteria:1. Signed informed consent must be obtained prior to participation in the study.2. Male or female subjects ≥18 years at Screening.3. Able to communicate well with the investigator, understand and comply with the requirements of the study.4. Newly-diagnosed or relapsed GPA and MPA (according to the 2022 ACR / EULAR classification criteria for GPA and MPA (Robson et al. 2022, Suppiah et al. 2022)) requiring treatment with RTX and GC as per investigator's judgement.5. BVAS assessment with ≥1 major item, or ≥3 minor items, or ≥2 renal items at Screening.6. Positive test of anti-PR3 or anti-MPO antibodies at Screening or with history of documented evidence of a positive test.7. Patient willing to comply with antibiotic prophylaxis effective against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.8. Circulating IgG > 4.0 g / L. Exclusion CriteriaPotential participants meeting any of the following criteria are not eligible for inclusion in this study.1. Other systemic disease which constitutes the primary illness, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), moderate to severe systemic lupus erythematosus, IgA vasculitis (Purpura Schönlein-Henoch), rheumatoid vasculitis, Sjögren's syndrome, anti-glomerular basement membrane (GBM) disease, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome or mixed connective tissue disease.2. Alveolar hemorrhage requiring invasive pulmonary ventilation support at Screening.3. Severe kidney disease defined as estimated glomerular filtration rate <15 mL / min / 1.73m2, or kidney failure defined as receiving renal replacement therapy such as hemo(dia)filtration, hemo- / peritoneal dialysis, or having received a kidney transplant.4. Received plasma exchange / -pheresis within 12 weeks prior to Screening.5. Received any of the following immunosuppressive, cell depleting or biological therapy (any other immunosuppressive, cell depleting, or biological therapy not listed here must be discussed with the Sponsor):Received RTX or other B-cell depleting agent within 16 weeks prior to Screening.Received any of the following biological or alkylating immunosuppressive medications within 12 weeks before screening, including but not limited to:cyclophosphamide (CYC)complement inhibitor (such as eculizumab, avacopan)anti-tumor necrosis factor treatmentabatacepttocilizumabintravenous immunoglobulinsReceived any of the following cell depleting agents within 24 weeks before Screening, including but not limited to:alemtuzumabantithymocyte globulinReceived azathioprine (AZA), methotrexate (MTX), or mycophenolate (MMF), or any other immunosuppressants with similar half-life) within 1 week prior to Day 1.Received leflunomide (LEF) within 6 weeks prior to Day 1.6. Received >1500 mg cumulative intravenous methylprednisolone or equivalent within 2 weeks before Randomization.7. Received chronic daily oral GC dose >10 mg prednisone-equivalent for more than 6 weeks prior to Screening, or daily dose oral GC dose >75 mg prednisone-equivalent within 2 weeks before Screening.8. Received a live vaccination within 4 weeks prior to Day 1 or planned between Screening and Week 24.9. Currently taking a strong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John’s wort.10. A history of recurrent invasive infections caused by encapsulated organisms (e.g., N. meningitidis and S. pneumoniae).11. Participants with an active systemic bacterial, viral, fungal or parasite infection that required use of intravenous antibacterials, antivirals, antifungals, or anti-parasitic agents within 30 days of Screening.12. Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV at Screening).13. Active infection with Hepatitis B (HBV) or Hepatitis C (HCV), defined as either HBV surface antigen (HBsAg) positive or HBV DNA, or HCV RNA positive, or latent infections defined as HBsAg is negative but HBV core antibody (HBcAb) positive.14. Evidence of either active or latent tuberculosis according to local standard by either based on QuantiFERON assay or T-SPOT or purified protein derivative (PPD) skin test, or chest radiography, performed at Screening or within 2 months prior to Screening.15. History of malignancy of any organ system within the 5 years prior to Screening, with the exception of excised basal cell carcinoma of the skin, or in situ carcinoma such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.16. Any one of the following laboratory values at Screening:White blood cells (WBC) count <2.0 x 103 / μlNeutrophil count <1.0 x 103 / μlAlanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times the upper limit of normal (ULN)Total bilirubin >3 x ULN (with the exception of those participants with a known confirmed diagnosis of Gilbert syndrome)17. History of hypersensitivity to any of the study treatments or excipients, or to drugs of similar chemical classes.18. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.19. Pregnant or nursing (lactating) women.20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for 1 week after stopping of study treatment. Effective contraception methods include:Total abstinence when this is in line with the preferred and usual lifestyle of the participant. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.Barrier methods of contraception: Condom or Occlusive cap (e.g. diaphragm or cervical / vault caps) with spermicidal foam / gel / film / cream / vaginal suppositoryUse of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.If local regulations are more stringent than the contraception methods listed above, local regulations apply and will be described in the ICF.Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age-appropriate history of vasomotor symptoms). Women participants are considered not of child-bearing potential if they are post-menopausal or have had bilateral tubal ligation, surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks prior to first dose of study treatment on study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is not considered to be of child-bearing potential. Study Treatment(s) and concomitant therapyDescription of study treatment(s) and treatment armsTreatments for each group are shown in Table 3. Table 3 Description of study treatment(s) and treatment armsArmTreatmentScreening periodInduction periodMaintenance period(open label)ExperimentalIptacopan-200 mg BID, oral200 mg BID, oralGlucocorticoid≤1500 mg cumulative IV methylprednisolone or equivalent within 2 weeks before RandomizationStart with ≤75 mg / day prednisone tapering to ≤5 mg / day after Week 16≤5 mg / day oral prednisoneRituximab-1000 mg IV at Day 1 and Week 2, or 375 mg / m2 once weekly for 4 weeks starting from Day 1Rescue medicationAntibiotic prophylaxis-Antibiotic prophylaxis effective against Pneumocystis jirovecii pneumonia, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzaeControlIptacopan matching placebo-0 mg BID oral-Glucocorticoid≤1500 mg cumulative IV methylprednisolone or equivalent within 2 weeks before RandomizationStart with ≤75 mg / day prednisone tapering to ≤5 mg / day after Week 16≤5mg / day oral prednisoneRituximab-1000 mg IV at Day 1 and Week 2, or 375 mg / m2 once weekly for 4 weeks starting from Day 1Control arm: 500 – 1000 mg after Week 24 visitAntibiotic prophylaxis-Antibiotic prophylaxis effective against Pneumocystis jirovecii pneumonia, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzaeAntibiotic prophylaxis against Pneumocystis jirovecii pneumonia The investigational drug, iptacopan (LNP023) as 200 mg and matching placebo capsules, will be prepared and supplied to investigator sites as double-blind participant kits for the Induction period.Additionally, the investigational drug, iptacopan (LNP023) as 200 mg capsules, will be prepared and supplied to investigator sites as open-label participant kits for the Maintenance period.RTX and GC, used as standard of care medications, are considered as AxMP and will be provided by the investigational site as per current guidelines for treating GPA and MPA AAV. Table 4. Investigational and control drugTreatment titleInduction periodiptacopan 200 mgInduction periodiptacopan matching placebo 0 mgMaintenance periodiptacopan 200 mgTreatment descriptionCapsule 200 mg, BIDCapsule 0 mg, BIDCapsule 200 mg, BIDTypeInvestigational drugInvestigational drugInvestigational drugDose formulationcapsulecapsulecapsuleUnit dose strength(s)200 mg0 mg200 mgDosage level(s)200 mg, BID0 mg, BID200 mg, BIDRoute of administrationoraloraloralUseexperimentalplaceboexperimentalIMPyesyesyesSourcingprovided centrally by the Sponsorprovided centrally by the SponsorProvided centrally by the SponsorPackaging and labelingdouble blind [during Induction period, then open label during Maintenance period].Double blind treatment will be provided in bottles of 70 capsules. Each bottle will be labeled as required per country requirement.double blind [during Induction period]. Double blind treatment will be provided in bottles of 70 capsules. Each bottle will be labeled as required per country requirement.open label [during Maintenance period].Open label treatment will be provided in bottles of 70 capsules. Each bottle will be labeled as required per country requirement. The investigational drug, iptacopan as 200 mg and matching placebo capsules, will be supplied to investigator sites as double-blind participant kits. Additional study treatmentsTable 5 Additional study treatmentTreatment titleRituximabPrednisoneMethylprednisoloneTreatment descriptioninjectiontabletinjectionTypebiologicdrugdrugDose formulationvialtabletvialUnit dose strength(s)10 mg / mL1, 2, 2.5, 5, 10, 20 mg or other dose strengths as specified in the label40, 62.5, 80, 125  mg / ml (when mixed), or other dose strengths as specified in the labelDosage level(s)Induction period: 1000 mg IV at Day 1 and Week 2, or 375 mg / m2 once weekly for 4 weeks starting from Day 1Maintenance phase:Control arm: 500 – 1000 mg after Week 24 visitRefer to Table 6 for GC tapering schedule and Rescue medication≤1500 mg IV prior to randomizationRoute of administrationIV infusionoralIV infusionUseSOCSOC and rescue medicationSOCAuthorization status of the AxMP in EEAyesyesyesSourcingprovided locally by the study siteprovided locally by the study siteprovided locally by the study sitePackaging and labelingNANANA RTX inductionAfter Randomization, all participants will receive either four (4) or two (2) consecutive, IV RTX doses as per center preference. Participants receiving 4 doses will be administered RTX IV at 375 mg / m2 every 7 days for 4 weeks. Participants receiving 2 doses will be administered RTX 1000 mg IV at Day 1 and subsequently at the Week 2 study visit. RTX during Maintenance periodAfter the Week 24 study visit, participants in the Control arm will receive RTX at dose levels 500 – 1000 mg IV as per center preference.Participants receiving iptacopan will not receive RTX in Maintenance period.Study participants who did not achieve complete remission (BVAS=0) during the Induction period will be considered treatment failures, and may be re-treated with RTX or other relevant medication at the discretion of the investigator. Participants with treatment failure should remain in the study and continue receiving the study treatment, unless otherwise specified in Section 7 for treatment discontinuation. GC treatmentGC use of ≤1500 mg IV methylprednisolone equivalent prior to Randomization is acceptable.During the Screening period, participants can take up to 75 mg / day oral prednisone equivalent. From Day 1. PO GC therapy will be used with dose levels ranging from 40 mg / day to 75 mg / day to, as per investigator's discretion, and will be tapered to ≤5 mg / day during a 16-week period as per the protocol defined schedule (Table 6). Dosing schedule for GC tapering (daily dose)Day (Week)Daily prednisone equivalent dose [mg / day]Day 1 to 7(Week 1)40506075Day 8 to 14 (Week 2)30404550Day 22 (Week 3)20253035Day 28 (Week 4)20253030Day 29 to 42 (Week 5-6)15152020Day 43 to 56 (Week 7-8)10101515Day 57 to 70 (Week 9-10)7.57.51010Day 71 to 84 (Week 11-12)5.05.07.57.5Day 85 to 98 (Week 13-14)2.52.555Day 99 to 112 (Week 15-16)≤2.5≤2.52.52.5> Week 16≤5.0≤5.0≤5.0≤5.0 Study participants will continue with a GC dose ranging from 0 to 5 mg / day after Week 16 until end of treatment visit (Week 48). Vaccination (iptacopan arm only) at Week 40Participants who received iptacopan during the Induction and Maintenance periods with no RTX re-dosing until Week 40 will be vaccinated against N. meningitidis, S. pneumoniae, and H. influenzae at the Week 40 study visit.Antibiotic prophylaxis against N. meningitidis, S. pneumoniae, and H. influenzae will be continued until at least Week 48 study visit when the serological response to vaccination will be evaluated.Vaccines should cover as many serotypes as possible (including meningococcal serotypes A, C, Y, W-135 and B). To minimize participant's burden, the use of multivalent vaccines is recommended as locally available and per local guidelines and regulations (e.g., quadrivalent vaccine for N.meningitidis which covers serotypes A, C, Y and W-135; and Pneumovas-23 which covers 23 S.pneumoniae serotypes). For the vaccination type and booster requirements, local guidelines and locally available vaccines should be used (and refer to the package insert of those or local guidelines). Use of antibiotic prophylaxisStudy participants treated with RTX and / or high dose of GC should receive antibiotic prophylaxis against Pneumocystis jirovecii pneumonia and other infections (Chung et al. 2021, Hellmich et al. 2023). Trimethoprim–sulfamethoxazole can be used as antibiotic prophylaxis against both, P. jirovecii pneumonia and S. pneumoniae and H. influenzae in this study.Study participants will additionally receive antibiotic prophylaxis against N. meningitidis according to local practice. As recommended by the Centers for Disease Control and Prevention (CDC), ciprofloxacin and ceftriaxone are acceptable antimicrobial agents for short-term prophylaxis against N. meningitidis. Penicillin and amoxycillin can be considered as chronic antibiotic prophylaxis against meningitis. Penicillin V has been recommended as the first-line antibiotic prophylaxis treatment against N. meningitidis in complement deficiencies (Bai et al. 2019), and it is narrow-spectrum antibiotics. Macrolides such as erythromycin is suggested for penicillin-allergic participants (McNamara et al. 2017 HCSP 2014).During the Maintenance period, antibiotic prophylaxis effective against S. pneumoniae, N. meningitidis, and H. influenzae are not mandated in the Control group; however, participants in the Control group may continue receiving antibiotic prophylaxis against Pneumocystis jirovecii pneumonia infections according to local practice. Treatment arms / groupParticipants will be assigned at visit Day 1 (Randomization visit) to one of the following experimental (iptacopan) or control (placebo) treatment arms / groups in a ratio of 1:1:Experimental (iptacopan)Iptacopan orally at 200 mg capsules BID (AM and PM) for 24 weeks in the Induction period followed by open label iptacopan 200 mg capsules BID for an additional 24 weeks in the Maintenance period.Control (placebo)Placebo orally at 0 mg capsules BID (AM and PM) for 24 weeks in the Induction period. Table 7 Treatment arm(s) Iptacopan 200 mgPlacebo 0 mgArm typeinvestigational drug, active iptacopan 200 mg BID [daily]investigational drug, placebo placebo 0 mg BID [daily]Arm description200 mg BID0 mg BIDAssociated treatment labelsiptacopan (LNP023) 200 mg BIDIptacopan (LNP023) matching placebo 0 mg BID  Instruction for prescribing and taking study treatmentTable 8 Dose and treatment schedule Investigational DrugDose per intakeFrequency and / or RegimenIptacopan 200 mg200 mg (one 200 mg hard gelatin capsule)Twice per day (200 mg dose once in the morning and once in the evening) All kits of study treatment assigned by the IRT will be recorded in the IRT system.Participants should be instructed to swallow whole capsules and not to chew or open them.Participants should take iptacopan twice daily at approximately the same time each day in the morning and in the evening and ideally with 12-hours interval between morning and evening dosing. On days that pharmacokinetic (PK) samples are obtained, the participant should take iptacopan during the clinic visit after the pre-dose PK blood sample when instructed by the study staff.Participants should take iptacopan without regard to food. Each dose may be taken with a glass of water.If vomiting occurs during the course of treatment, participants should not take iptacopan again before the next scheduled dose.Participants should be instructed not to make up missed doses. A missed dose is defined as a case when the full dose is not taken within 8 hours after the approximate time of the usual daily dosing. That day's dose should be omitted, and the participant should continue treatment with the next scheduled dose.Participants should be instructed to inform study personnel of all dates of missed doses so that study treatment compliance can be determined at each visit. Measures to minimize bias: randomization and blindingThe randomization numbers will be generated using the procedure to ensure that treatment assignment is unbiased and concealed from participants and Investigator staff.Randomization will be stratified by GPA or MPA, disease status (newly diagnosed or relapsed AAV) and renal status with a threshold of eGFR at 45 ml / min / 1.73 m2. Dose escalationsIptacopan or matching placebo will be administered at a dose of 200 mg BID. Dose change and adjustments in dosing frequency are not permitted. Concomitant therapiesStandard of care consists of RTX and intravenous / oral glucocorticoid.All medications, procedures, and significant non-drug therapies (including physical therapy and blood transfusions) administered after the participant was enrolled into the study must be recorded on the appropriate CRF.Each concomitant drug must be individually assessed against all exclusion criteria and prohibited medication.. Prohibited therapiesUse of the treatments displayed in Table 9 are not allowed during the prohibition period. Table 9 Prohibited medication MedicationProhibition periodAction takenLive vaccinationFrom 4 weeks prior to randomization until the end of the studyDiscontinue study treatmentB cell depleting agent other than RTXFrom 16 weeks prior to screening until the end of treatment periodDiscontinue study treatmentCyclophosphamideFrom 12 weeks to screening until the end of treatment periodDiscontinue study treatmentIntravenous immunoglobulinFrom 12 weeks to screening until the end of treatment periodStudy participant maybe discontinued from study treatment in a case-by-case basisComplement inhibitor other than iptacopan (such as eculizumab, avacopan, etc.)From 12 weeks to screening until the end of treatment periodDiscontinue study treatmentAny other cell depleting agents including but not limited to alemtuzumab, antithymocyte globulinFrom 24 weeks to screening until the end of treatment periodDiscontinue study treatmentAny other biological immunosuppressive therapy including but not limited to anti-tumor necrosis factor treatment, abatacept, tocilizumab,From 12 weeks to screening until the end of treatment periodDiscontinue study treatmentAZA, MMF or MTXFrom 1 week to randomization until the end of treatment periodStudy participant maybe discontinued from study treatment in a case-by-case basisLEFFrom 6 weeks to randomization until the end of treatment periodStudy participant maybe discontinued from study treatment in a case-by-case basisStrong inducer of the cytochrome P450 3A4 (CYP3A4) enzyme, such as carbamazepine, phenobarbital, phenytoin, rifampin, or St. John’s wort*From screening until the end of treatment periodStudy participant maybe discontinued from study treatment in a case-by-case basis* Strong CYP3A4 inducers have a potential to reduce the systemic exposure of GCs which are CYP3A4 substrates. Rescue medicationPatients who experienced worsening during Induction period (up to week 20) may be treated with a short burst of GC, defined as additional oral GCs > 5 mg / day and ≤ 20 mg / day (prednisone-equivalent) for a maximum of 7 days at the discretion of the investigator.Patients who experienced worsening during Maintenance period, may be treated with no more than two short bursts of GC, defined as additional oral GCs > 5mg / day and ≤ 20 mg / day (prednisone equivalent) for maximum 14 days for each burst at the discretion of the investigator.If there is deterioration or no improvement in BVAS during the planned GC tapering phase, it is at the discretion of the investigator to administer rescue medication.Participants who received iptacopan may receive RTX as a rescue medication only if they are at risk of relapse based on:BVAS >0 or clinical symptoms indicating relapse, and / orReoccurrence after being negative, or a >2-fold increase of anti-PR3 or anti-MPO antibodies from lowest level.The administration or the receipt of rescue therapy for lack of efficacy or relapses do not necessarily discontinue the study participants from further study treatment administration or from study participation. Please refer below for treatment discontinuation. The rescue therapy will not be provided by the sponsor.At the time a major or minor relapse is suspected by the study participants, they have to visit the study center for an unscheduled visit.Oral GC ≤5 mg for AAV will not be considered as rescue medication. Discontinuation of study treatment and participantdiscontinuation / withdrawalDiscontinuation of study treatment for a participant occurs when study treatment is permanently stopped for any reason (prior to the planned completion of study treatment administration) and can be initiated by either the participant or the Investigator.The Investigator must discontinue study treatment for a given participant if they believe that continuation would negatively impact the participant's well-being.Discontinuation from study treatment is required under the following circumstances:Participant / guardian decisionPregnancyUse of certain prohibited medication as per recommendationsAny situation in which continued study participation might result in a safety risk.Following emergency unblinding Occurrence of one of the following events:1. Bacterial sepsis, meningococcal, pneumococcal or H.influenzae infection as confirmed by bacterial cultures2. A participant's eGFR falls to <15 ml / min / 1.73m2 and confirmed after repeated test 4 weeks later3. The initiation of renal replacement therapy (hemofiltration, dialysis)4. The need of kidney transplantation5. Plasma exchangeAny laboratory abnormalities that in the judgment of the Investigator, taking into consideration the participant’s overall status, prevents the participant from continuing participation in the study. Study assessments and proceduresEfficacy assessments Birmingham Vasculitis Activity Score Version 3.0 (BVASv3)The impact of iptacopan on GPA and MPA will be assessed by BVASv3. The BVASv3 is a validated instrument for the assessment of disease activity and response to treatment in AAV (Mukhtyar et al. 2009).The BVASv3 form is a list of 56 items with a numerical weight attached to each item, and with each organ system having a ceiling score. These scores reflect the proportional importance of each manifestation and each organ system. The form is divided into 9 organ-based systems, with each section including symptoms / signs that are typical of that particular organ involvement in systemic vasculitis. All items are to be scored at every visit with the exception of creatinine levels, which are only scored at the study participant’s first assessment. Completion of the form provides a numerical score by using the Glossary and Scoring for the BVASv3 (Table 10), with  higher scores indicating more severe disease.Table 10 BVASv3 glossary and scoring system per body system and itemSystem / itemDescriptionNew / Worse scorePersistent score1. GeneralMax Score32MyalgiaPain in the muscles11Arthralgia or arthritisPain in the joints or joint inflammation11Fever ≥ 38.0 0CDocumented oral / axillary temperature elevation. Rectal temps are 0.5 0C higher22Weight LossAt least 2kg loss of body weight (not fluid) having occurred since last assessment or in the 4 weeks not as a consequence of dieting222. CutaneousMax Score63InfarctArea of tissue necrosis or splinter haemorrhages21PurpuraPetechiae (small red spots), palpable purpura, or ecchymoses (large plaques) in skin or oozing (in the absence of trauma) in the mucous membranes.21UlcerOpen sore in a skin surface.41GangreneExtensive tissue necrosis (e.g. digit)62Other skin vasculitisLivedo reticularis, subcutaneous nodules, erythema nodosum, etc213. Mucous membranes / eyesMax Score63Mouth ulcers / granulomataAphthous stomatitis, deep ulcers and / or “strawberry” gingival hyperplasia, excluding lupus erythematosus, and infection21Genital ulcersUlcers localized in the genitalia or perineum, excluding infections.11Adnexal inflammationSalivary (diffuse, tender swelling unrelated to meals) or lacrimal gland inflammation. Exclude other causes (infection). Specialist opinion may be required.42Significant proptosisProtrusion of the eyeball due to significant amounts of inflammatory in the orbit; if unilateral, there should be a difference of 2 mm between one eye and the other. This may be associated with diplopia due to infiltration of extra-ocular muscles. Developing myopia (measured on best visual acuity, see later) can also be a manifestation ofproptosis42Red eye (Epi)scleritisInflammation of the sclerae (specialist opinion usually required). Can be heralded by photophobia.21Red eye conjunctivitisInflammation of the conjunctivae (exclude infectious causes and excluding uveitis as cause of red eye, also exclude conjunctivitis sicca which should not be scored as this is not a feature of active vasculitis); (specialist opinion not usually required).11BlepharitisInflammation of eyelids. Exclude other causes (trauma, infection). Usually no specialist opinion is requiredKeratitisInflammation of central or peripheral cornea as evaluated by specialistBlurred visionAltered measurement of best visual acuity from previous or baseline, requiring specialist opinion for further evaluation.32Sudden visual lossSudden loss of vision requiring ophthalmological assessment.6*UveitisInflammation of the uvea (iris, ciliary body, choroid) confirmed by ophthalmologist.62Retinal vasculitisRetinal vessel sheathing on examination by specialist or confirmed by retinal fluorescein angiography62Retinal vessel thrombosisArterial or venous retinal blood vessel occlusionRetinal exudatesAny area of soft retinal exudates (exclude hard exudates) seen on ophthalmoscopic examination.Retinal haemorrhagesAny area of retinal haemorrhage seen on ophthalmoscopic examination.4. ENTMax Score63Bloody nasal discharge / nasal crusts / ulcers and / or granulomataBloody, mucopurulent, nasal secretion, light or dark brown crusts frequently obstructing the nose, nasal ulcers and / or granulomatous lesions observed by rhinoscopy42Paranasal sinus involvementTenderness or pain over paranasal sinuses with pathologic imaging (CT, MR, x-ray).21Subglottic stenosisStridor and hoarseness due to inflammation and narrowing of the subglottic area observed by laryngoscopy63Conductive hearing lossHearing loss due to middle ear involvement confirmed by otoscopy and / or tuning fork examination and / or audiometry31Sensorineural hearing lossHearing loss due to auditory nerve or cochlear damage confirmed by audiometry625. ChestMax Score63WheezeWheeze on clinical examination21Nodules or cavitiesNew lesions, detected by imaging.3*Pleural effusion / pleurisyPleural pain and / or friction rub on clinical assessment or new onset of radiologically confirmed pleural effusion. Other causes (e.g. infection, malignancy) should be excluded42InfiltrateDetected by CXR or CT scan. Other causes (infection) should be excluded42Endobronchial involvementEndobronchial pseudotumor or ulcerative lesions. Other causes such as infection or malignancy should be excluded. NB: smooth stenotic lesions to be included in VDI; subglottic lesions to be recorded in the ENT section.42Massive haemoptysis / alveolar haemorrhageMajor pulmonary bleeding, with extensive pulmonary infiltrates; other causes of bleeding should be excluded if possible. Patients are usually in extremis. Do not record minor episodes of haemoptysis.64Respiratory failureDyspnoea which is sufficiently severe as to require artificial ventilation646. CardiovascularMax Score63Loss of pulsesLoss of pulses in any vessel detected clinically; this may include loss of pulses leading to threatened loss of limb41Valvular heart diseaseSignificant valve abnormalities in the aortic mitral or pulmonary valves detected clinically or echocardiographically.42PericarditisPericardial pain & / or friction rub on clinical assessment.31Ischaemic cardiac painTypical clinical history of cardiac pain leading to myocardial infarction or angina. Consider the possibility of more common causes (e.g. atherosclerosis)42CardiomyopathySignificant impairment of cardiac function due to poor ventricular wall motion confirmed on echocardiography63Congestive cardiac failureHeart failure by history or clinical examination637. AbdominalMax Score94PeritonismAcute abdominal pain with peritonism / peritonitis due to perforation / infarction of small bowel, appendix or gallbladder etc., or acute pancreatitis confirmed by radiology / surgery / elevated amylase93Bloody diarrhoeaOf recent onset; inflammatory bowel disease and infectious causes excluded.93Ischaemic abdominal painSevere abdominal pain with typical features of ischaemia confirmed by imaging or at surgery, with typical appearances of aneurysms or abnormal vasculature characteristic of vasculitis.628. RenalMax Score126HypertensionSystolic BP>140 or Diastolic BP>95, accelerated or not, with or without retinal changes.41Proteinuria>1+ on urinalysis; >0.2g / 24 hours Infection should be excluded.42Haematuria10 or more RBC per hpf ( high power field ), excluding urinary infection and urinary lithiasis (stone)or drug side effects (e.g. cyclophosphamide)63Creatinine 125-249Serum creatinine values 125-249 μmol / l (1.41-2.82 mg / dL); only used at first assessment.4*Creatinine 250-499Serum creatinine values 250-499 μmol / l (2.83-5.64 mg / dL); only used at first assessment.6*Creatinine ≥ 500Serum creatinine values 500 μmol / l(≥5.66mg / dL) or greater; only used at first assessment.8*Rise in serum creatinine> 30% or creatinine clearance fall > 25%Significant deterioration in renal function attributable to active vasculitis.6*9. Nervous systemMax Score96HeadacheNew, unaccustomed & persistent headache11MeningitisSevere headache with neck stiffness ascribed to inflammatory meningitis after excluding infection / bleeding31Organic confusionImpaired orientation, memory or other intellectual function in the absence of metabolic, psychiatric, pharmacological or toxic causes.31Seizures (not hypertensive)Paroxysmal electrical discharges in the brain & producing characteristic physical changes including tonic & clonic movements & certain behavioural changes.93StrokeCerebrovascular accident resulting in focal neurological signs such as paresis, weakness, etc. A stroke due to other causes (e.g. atherosclerosis) should be considered & appropriate neurological advice is recommended93Cord lesionTransverse myelitis with lower extremity weakness or sensory loss (usually with a detectable sensory level) with loss of sphincter control (rectal & urinary bladder).93Cranial nerve palsyFacial nerve palsy, recurrent nerve palsy, oculomotor nerve palsy etc. excluding sensorineural hearing loss and ophthalmic symptoms due to inflammation63Sensory peripheral neuropathySensory neuropathy resulting in glove & / or stocking distribution of sensory loss. Other causes should be excluded (e.g. idiopathic, metabolic, vitamin deficiencies, infectious, toxic, hereditary).63Motor mononeuritis multiplexSimultaneous neuritis of peripheral nerves, only scored if motor involvement. Other causes should be excluded (diabetes, sarcoidosis, carcinoma, amyloidosis).9310. OtherOther features of active vasculitis-please describe. Remember that you should review the rest of the BVAS item list before writing the feature in this section because it may already have been described elsewhere on the form. Do not use this section to record laboratory, imaging or pathology findings. Items recorded in this section will not carry any value when calculating the BVAS score00Mukhtyar et al. 2008*For some BVAS items, no recording or scoring of persistent items is provided, either because the item is by definition new / worse, or for renal disease, can only reliably be recorded as new / worse on the first visitMajor items are indicated in bold and italic. To standardize the BVASv3 assessment in this study, the same investigator should score the study participants at all visits, if possible.In order to use and score the form properly, all investigators performing the BVASv3 assessment must be certified. Training and specific instructions on the use of BVASv3 for this study will be provided to sites. BVASv3 assessments will be made by Investigators. The sponsor will review BVAS scoring performed by sites for data quality and accuracy purposes. This review might involve experts in the field.In this study, remission status of study participants will be evaluated using BVASv3.Complete remission is defined as having a BVASv3 score of 0 and taking a dose of GC lower than or equal to 5mg / day within 4 weeks prior to the timepoint of assessment.Sustained remission at Week 48 is defined as complete remission at Week 24 and no major relapse until Week 48. Vasculitis Damage Index (VDI)The VDI will be used to assess damage induced by GPA or MPA and by the treatments applied during this study. The VDI is a validated assessment tool for recording organ damage that has occurred in patients since the onset of vasculitis (Exley et al. 1997). The VDI is comprised of 64 items of damage divided into 11 organ-based systems (Section 10.6.2). Each item scores 1 point. The VDI is used to record any condition that has been present for at least 3 months since the onset of vasculitis, even in case they subsequently resolve and regardless of being attributable directly to the vasculitis or not. All damage that occurred after the onset of the first symptoms related to the vasculitis will be scored, regardless of the cause. The number of positive items is added for the total VDI score. Finally, the VDI was constructed to be a cumulative index; any previously scored items on the VDI must be carried forward to subsequent visits. Therefore, the VDI score could not decrease over time. To avoid any possible bias the VDI assessment in this study, the same investigator should score the subject at all visits, if possible. The sponsor will review VDI assessment performed by sites to verify data quality and accuracy. This review might involve experts in the field. Glucocorticoid Toxicity Index (GTI)A Glucocorticoid Toxicity Index (GTI) has been developed as a comprehensive GC toxicity assessment instrument (Miloslavsky et al. 2017) and most recently reviewed (Stone et al. 2022). The GTI can be used across disciplines to assess the clinical value of steroid-sparing therapies, as well as to measure the impact of GC toxicity. A Composite GTI and Specific List comprise the overall GTI. The Composite GTI reflects toxicity likely to change during a clinical trial. The Composite GTI toxicities occur commonly, vary with GC exposure, and are weighted and scored. Relative weights for items in the Composite GTI were derived by group consensus and multi-criteria decision analyses. The Specific List was designed to capture GC toxicity not included in the Composite GTI. The bone domain is excluded since the treatment period is no more than 1 year in duration.The GTI provides two scores: the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS). With the AIS, toxicities can be removed if improvement occurs (and added if worsening occurs). The AIS is important in establishing that a new therapy is effective and diminishes baseline GC toxicity over time. The CWS is designed to assess cumulative GC toxicity, regardless of whether the toxicity has lasting effects or is transient. New toxicities that occur are added, but toxicities that appear to resolve on follow-up are not removed. The CWS serves as a record of GC toxicity observed and can only increase or remain the same over time.The components of Composite GTI and scoring as well as the component of Specific List are provided in Table 11. Definitions of individual items are provided in the original publication (Miloslavsky et al. 2017). Table 11 GTI scores per itemScoring ItemScore1. Change in Body Weight (BMI)Decrease by > / = 5 BMI units-36Decrease by >2 but <5 BMI units-21No significant change (+ / - 2 BMI units)0Increase of >2 to <5 BMI units21Increase of 5 or more BMI units362. Glucose MetabolismImprovement in HbA1c AND decrease in medication-44Improvement in HbA1c OR decrease in medication-32No significant change0Increase in HbA1c OR increase in medication32Increase in HbA1c AND increase in medication443. Blood PressureImprovement in BP AND decrease in medication-44Improvement in BP OR decrease in medication-19No significant change0Increase in BP OR increase in medication19Increase in BP AND increase in medication444. HyperlipidemiaDecrease in LDL AND decrease in medication-30Decrease in LDL OR decrease in medication-10No significant change0Increase in LDL OR increase in medication10Increase in LDL AND increase in medication305. Steroid MyopathyModerate weakness to none-63Moderate to Mild weakness-54Mild weakness to none-9No significant change0None to Mild weakness (without functional limitation)9Mild to Moderate weakness54None to Moderate weakness (with functional limitation)636. Skin steroid-related ToxicityDecrease in Skin Toxicity - Moderate to None-26Decrease in Skin Toxicity - Moderate to Mild-18Decrease in Skin Toxicity - Mild to None-8No significant change0Increase in Skin Toxicity - None to Mild8Increase in Skin Toxicity - Mild to Moderate18Increase in Skin Toxicity - None to Moderate267. Neuropsychiatric - steroid related symptomsDecrease in NP Toxicity - Moderate to None-74Decrease in NP Toxicity - Moderate to Mild-63Decrease in NP Toxicity - Mild to None-11No significant change0Increase in NP Toxicity - None to Mild11Increase in NP Toxicity - Mild to Moderate63Increase in NP Toxicity - None to Moderate748. InfectionNo infection0Oral or vaginal candidiasis or non-complicated zoster (<Grade3)19Grade 3, 4, or 5 infections93Miloslavsky et al. 2017 First morning void (FMV), spot and eGFRFirst morning void (FMV) midstream urine samples will be collected at visits as described. Patients should collect the FMV at home on the morning of the study visit and bring with them to the clinic. The collected urine samples should be refrigerated after collection and before being taken to the clinic or laboratory. UACR (urinary albumin:creatinine ratio) and UPCR (urinary protein:creatinine ratio) will be calculated at the time points when the respective single urinary parameters are planned to be assessed.Serum creatinine, as part of the clinical chemistry panel through the central laboratory, will be used to calculate the eGFR applying the CKD-EPI formula. At Screening, either CKD-EPI formula or a modified Modification of Diet in Renal Disease (MDRD) formula may be applied according to specific ethnic groups and local guidelines.Hematuria will be evaluated via Spot Urinalysis. Appropriateness of efficacy assessmentsBVASv3 assessment is the most widely accepted validated measure of activity in ANCA-associated vasculitis, and its use is recommended by EULAR to standardize the evaluation of clinical trials in this indication. This scoring system allows the assessment of disease activity, the definition of trial entry criteria, remission, and relapse, as well as the measurement of patient’s outcomes.As opposed to the BVASv3 that evaluates disease activity, VDI assessment is a validated standardized clinical assessment of damage in vasculitis patients, allowing the tracking of damage evolution throughout the trial. This assessment has been widely used to evaluate damage by the disease itself, by side effects related to treatment or by any comorbidity that arise following vasculitis diagnosis. This is particularly important as the amount of damage experienced by patients correlates with an increased risk of mortality. The focus on identifying damage irrespective of causality can, therefore, help determine follow up strategies and interventions to safeguard patients, both due to the disease or to the treatment the patients are undergoing.GTI assessment serves as the primary instrument to quantify toxicities associated with GC use. It will therefore reflect the amount of cumulative GC dose and will further inform the effect of iptacopan.Urinary protein excretion, hematuria and eGFR are widely used measures of kidney function and indicators of disease progression. The 48 weeks of follow up provides an opportunity to assess the effect of iptacopan on kidney function. Safety assessmentsSafety assessments include physical examinations, electrocardiogram (ECGs), vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, coagulation and urinalysis), and adverse event (AE) monitoring.The risk of infections with encapsulated bacteria will be closely monitored throughout the study. Participant vigilance for early signs and symptoms of infection is required and supported by providing participants with a Participant Safety Card to enhance awareness and vigilance. PharmacokineticsPharmacokinetic samples will be collected at the visits defined in the assessment schedule. Only Ctrough samples will be collected. Follow instructions outlined in the Bioanalytics Study Specifications document regarding sample collection, numbering, processing and shipment.During induction period, pharmacokinetic samples will be obtained from all participants regardless of the treatment group to prevent unblinding. During maintenance period, pharmacokinetic samples will be obtained only from participants in the experimental arm (iptacopan arm). Samples will only be evaluated in participants receiving iptacopan.Iptacopan will be quantified in plasma by a validated LC-MS / MS method; the anticipated lower limit of quantification (LLOQ) is 1.0 ng / mL. Concentrations will be expressed in mass per volume units (ng / mL) and will refer to the free base.Concentrations below the LLOQ will be reported as “zero” and missing data will be labeled as such in the Bioanalytical Data Report.The first sample of the day will be collected immediately prior to taking the first daily iptacopan dose (pre-dose). The Investigator should remind the participant prior to the visit that during that specific visit the iptacopan dose will be administered at the site after the collection of the pre-dose PK blood sample.Iptacopan Ctrough concentrations will be determined. BiomarkersBiomarker analysis will be used to investigate the effect of iptacopan in AAV at the molecular and cellular level to determine how changes in the markers may relate to clinical outcomes, association with observed clinical responses and disease progression. In addition, disease markers and potential predictive markers of efficacy may be explored.While the goal of the biomarker assessments is to provide supportive data for the clinical study, there may be circumstances when a decision is made to stop a collection, or not perform or discontinue an analysis due to either practical or strategic reasons (e.g. inadequate sample number, issues related to the quality of the sample or issues related to the assay that preclude analysis, impossibility to perform correlative analyses, etc.). Therefore, depending on the results obtained during the study, sample analysis may be omitted.Samples will be collected as specified in the protocol.B cell counts and total IgG will be measured as part of secondary objectives to assess participant’s immune status.Other biomarkers studied as part of exploratory objectives may include, but are not limited to:• Biomarkers of the complement pathway activity / pharmacodynamic biomarkers: plasma and / or urine levels of complement fragment Bb of Factor B (Bb), C3a, sC5b-9, C5a; C3 in serum• Biomarkers of renal inflammation or pathology in urine: MCP-1, KIM-1, NGAL• Serum levels of anti-MPO and anti-PR3 antibodies as disease activity• B-cell subsets and other immune cells in blood• Lung and vascular injury markers • Total IgM The list of biomarkers may change during the course of the study due to new assay availability, technical issues or as more relevant biomarkers are determined during conduct of the iptacopan program. Biomarkers may also be analyzed retrospectively after closeout of the trial with decisions dependent on study outcome, new information on iptacopan's mechanism of action, and / or new biomarkers / proteins relevant to AAV.The sample collection information including exact time and date of collection must be entered on the appropriate sample collection CRF page(s) and requisition form(s). Follow instructions for sample collection, processing, and shipment provided in the laboratory manual. Profiling in plasma and / or urineSamples collected in plasma and urine may be investigated in multiplex hypothesis-free platforms to better understand iptacopan mode of action, the disease profile, or for markers that may be associated with treatment response or predict response to treatment. Optional GeneticsThe study includes an optional genetic research component which requires a separate informed consent signature if the participant agrees to participate. As permitted by local governing regulations and by IRB / EC, it is required as part of this protocol that the Investigator present these options to the participant.The purpose of genetic research may be to better understand the safety and efficacy of iptacopan, or to learn more about human diseases, or to help develop ways to detect, monitor and treat diseases.As technology changes over time, the most appropriate technology will be used at the time the exploratory genetic research is performed. This may include the study of the entire genome.Laboratory manuals will be provided with detailed information on sample collection, handling, and shipment. DNA samplesThe use of DNA to search for biomarkers of disease and drug action is exploratory. Any results from this DNA study will not be placed in the participant’s medical records. As an additional confidentiality measure, sample information is stored in one secured database while genetic data is stored in an independent secured database. Optional Additional ResearchIf the participant agrees, by signing the optional consent for Additional Research, biological samples and data that remain after analysis is completed may be used for additional research to help develop ways to detect, monitor or treat human diseases and / or learn more about related human diseases. A decision to perform such exploratory research studies would be based on outcome data from this study or from new scientific findings related to the drug class or disease, as well as assay availability. Adverse events (AEs), serious adverse events (SAEs), and other safety reportingDefinition and recording of adverse eventsAn AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.Any new or worsening findings, or relapse of AAV are to be recorded as adverse events and also captured in the BVAS, and or other questionnaire as appropriate.Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, accompanied by the following information (as far as possible):1. The severity grademild: usually transient in nature and generally not interfering with normal activitiesmoderate: sufficiently discomforting to interfere with normal activitiessevere: prevents normal activities2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression of underlying illness (i.e. progression of the study indication) the assessment of causality will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a lack of efficacy or progression of underlying illness are not caused by the trial drug, they happen in spite of its administration and / or both lack of efficacy and progression of underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a single participant. The investigator is obligated to assess the relationship between any treatment used in the study (study treatment, AxMP(s)) and each occurrence of each AE. The investigator will use clinical judgment to determine the relationship. A reasonable possibility of a relationship conveys that there are facts, evidence, and / or arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the temporal relationship of the event to study intervention administration, will be considered and investigated. For causality assessment, the investigator will also consult the IB and / or product information, for marketed products.  The causality assessment is one of the criteria used when determining regulatory reporting requirements. 3. Its duration (start and end dates or ongoing) and the outcome must be reported4. Whether it constitutes a SAE and which seriousness criteria have been met5. Action taken regarding with study treatment.All adverse events must be treated appropriately. Treatment may include one or more of the following:Dose not changededuced / increasedDrug interrupted / permanently discontinued6. Its outcomeConditions that were already present at the time of informed consent should be recorded in medical history of the participant.Adverse events (including lab abnormalities that constitute AEs) should be described using a diagnosis whenever possible, rather than individual underlying signs and symptoms.Adverse event monitoring should be continued until the EOS visit or until 7 days after early discontinuation, whichever is longer.Once an adverse event is detected, it must be followed until its resolution or until it is judged to be not recovered / not resolved (e.g. continuing at the end of the study), and assessment must be made at each visit (or more frequently, if necessary) of any changes in severity, the suspected relationship to the interventions required to treat it, and the outcome.Abnormal laboratory values or test results constitute adverse events only if they fulfill at least one of the following criteria:they induce clinical signs or symptomsthey are considered clinically significantthey require therapyClinically significant abnormal laboratory values or test results must be identified through a review of values outside of normal ranges / clinically notable ranges, significant changes from baseline or the previous visit, or values which are considered to be non-typical in participant with the underlying disease. Definition and recording of serious adverse events (SAE)An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following criteria:fatallife-threateningLife-threatening in the context of a SAE refers to a medical occurrence in which the participant was at risk of death at the time of the reaction; it does not refer to a medical occurrence that hypothetically might have caused death if it were more severe (please refer to the ICH-E2D Guidelines).results in persistent or significant disability / incapacityconstitutes a congenital anomaly / birth defect, fetal death or a congenital abnormality or birth defect.requires inpatient hospitalization or prolongation of existing hospitalization, unless hospitalization is for:routine treatment or monitoring of the studied indication, not associated with any deterioration in condition. elective or pre-planned treatment for a pre-existing condition that is unrelated to the indication under study and has not worsened since signing the informed consent.social reasons and respite care in the absence of any deterioration in the participant’s general conditiontreatment on an emergency outpatient basis for an event not fulfilling any of the definitions of a SAE given above and not resulting in hospital admission.is medically significant, e.g. defined as an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above.Medical and scientific judgment should be exercised in deciding whether other situations should be considered serious reactions, such as important medical events that might not be immediately life-threatening or result in death or hospitalization but might jeopardize the participant or might require intervention to prevent one of the other outcomes listed above. Such events should be considered as “medically significant.” Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization or development of dependency. Any suspected transmission via a medicinal product of an infectious agent is also considered a serious adverse reaction.All new malignant neoplasms will be assessed as serious under “medically significant” if other seriousness criteria are not met and the malignant neoplasm is not a disease progression of the study indication.Treatment-emergent elevations in AST or ALT (>3x ULN) in combination with total bilirubin >2x ULN or jaundice in the absence of cholestasis (defined as ALP < 2x ULN) or other causes of hyperbilirubinemia can be an indicator of severe drug induced liver injury (Hy’s Law). In patients with transaminases above the ULN at baseline, the Hy’s law criteria may be changed to increases 2-fold above baseline values. Statistical considerationsStatistical analysesAll inferential analyses will use 1-sided tests at 10% significance level and two-sided 80% confidence intervals.The stratification factors will include the phenotypes GPA or MPA, disease status (newly diagnosed or relapsed AAV) and renal status with a threshold of eGFR at 45 ml / min / 1.73m2.Categorical data will be presented as frequencies and percentages. For continuous data, mean, standard deviation, median, minimum, and maximum will be presented. For selected parameters, 25th and 75th percentiles will also be presented. Primary endpoint(s) / estimand(s) analysisThe primary aim of this study is to investigate the efficacy of iptacopan, as an add-on therapy to one cycle RTX and 16 weeks GC tapering for the treatment of newly diagnosed or relapsed patients with GPA and MPA vasculitis. Primary analysis will be performed with the PD analysis set. Definition of primary endpoint(s)Sustained remission at Week 48Sustained remission is defined as complete remission (BVAS=0 with a GC dose ≤5mg / day within Week 20 to Week 24) without major relapse up to Week 48. Statistical model, hypothesis, and method of analysisThe aim is to estimate the treatment effect of iptacopan as an add-on therapy to one cycle of RTX and 16 weeks GC tapering in maintaining remission at Week 48 compared to the control group. The following hypotheses will be tested to address the primary objective:H0 : p(iptacopan) – p(SOC) ≤ -0.2 VsH1 : p(iptacopan) – p(SOC) > -0.2where p is the proportion of responders.The experimental treatment (iptacopan arm) will be considered non-inferior to SOC if the null-hypothesis (H0) is rejected using a stratified Mantel–Haenszel test at one-sided 10% level of significance. The stratification will be based on the randomization stratification factors. Handling of intercurrent events of primary estimand (if applicable)The primary analysis will account for following intercurrent events:1. Discontinuation of study treatment for any reason: ignored (treatment policy strategy). All available data after discontinuation will be used as they are.2. Use of corticosteroids for any reason other than treatment of MPA or GPA at a dose exceeding an average of 20mg / day of prednisolone (or equivalent) for more than 14 days, except corticosteroids used for RTX pre-dosing: as if GC had not been administered (hypothetical strategy). An imputation procedure will be used to impute response at Week 48(after the intercurrent event).3. Any non-per protocol prescribed treatment to manage MPA or GPA (composite strategy). The participant will be considered as non-responder. Secondary endpoint(s) / estimand(s) analysisThe secondary objectives in this study are to evaluate participant immune status, complete remission, rapidity of response, relapse, renal functions, glucocorticoid sparing, safety, and participant QoL. Efficacy and / or pharmacodynamic endpoint(s)The PD analysis set will be used for the below analyses.B cell counts and total IgG levels will be summarized by means of descriptive statistics by visit and treatment group.The difference in proportion of patients on complete remission (BVAS=0 with a GC dose ≤5mg / day within Week 20 to Week 24) between the two groups will be calculated, along with its 80% confidence interval, using stratified Mantel–Haenszel test.Rapidity of response will be evaluated using time to reach a BVAS of 0, defined as the time from the date of first dose of study treatment to the first date when a BVAS of 0 is reached, regardless of whether the participants are receiving GCduring this period of time. Time to reach a BVAS of 0 will be censored if a BVAS of 0 is not observed. The censoring date will be the date of the last BVAS assessment.Time to reach a BVAS of 0 distribution will be estimated using the Kaplan-Meier method, and the Kaplan-Meier curves, medians and 80% confidence intervals of the medians will be presented for each treatment group. The hazard ratio for time to reach a BVAS of 0 will be calculated, along with its 80% confidence interval, using a stratified Cox model.Time to major relapse is defined as the time from the date of first dose of study treatment to the date of major relapse (refer to Table 2). Time to major relapse will be censored if a major relapse is not observed. The censoring date will be the date of the last BVAS assessment. Time to major relapse will be analyzed in a similar way as time to reach a BVAS of 0.Change from baseline in eGFR, albuminuria, and proteinuria (in patients with active renal disease at baseline) will be summarized by means of descriptive statistics by visit and treatment group.Cumulative and average daily GC dose will be summarized by means of descriptive statistics by visit and treatment group.Change in SF-36 v2 and physician / patient global assessments (Ph / PtGA) scores will be summarized by means of descriptive statistics by visit and treatment group. Safety endpointsFor all safety analyses, the safety set will be used. All listings and tables will be presented by treatment group.Safety summaries (tables, figures) include only data from the on-treatment period with the exception of baseline data which will also be summarized where appropriate (e.g., change from baseline summaries). In addition, a separate summary for death including on treatment and post treatment deaths will be provided. In particular, summary tables for adverse events (AEs) will summarize only on-treatment events, with a start date during the on-treatment period (treatment-emergent AEs).The on-treatment period lasts from the date of first administration of study treatment until 7 days after the date of the last actual administration of iptacopan. Adverse eventsAll information obtained on adverse events will be displayed by treatment group and participant.The number (and percentage) of participants with treatment emergent adverse events (events started after the first dose of study medication or events present prior to start of double-blind treatment but increased in severity based on preferred term) will be summarized in the following ways:by treatment, primary system organ class and preferred term.by treatment, primary system organ class, preferred term and maximum severity.by treatment and preferred term.Separate summaries will be provided for study medication related adverse events, death, serious adverse events, other significant adverse events leading to discontinuation.The number (and proportion) of participants with adverse events of special interest / related to identified and potential risks will be summarized by treatment.A participant with multiple adverse events within a primary system organ class is only counted once towards the total of the primary system organ class. Vital signsAll vital signs data will be summarized by treatment and visit / time. If ranges are available, abnormalities will be listed by treatment group, participant and visit / time point. Summary of notable vital sign values / abnormalities may be provided by treatment. 12-lead ECGPR, QRS, QT, QTcF, and RR intervals will be obtained from 12-lead ECGs for each participant during the study.Categorical Analysis of QT / QTc interval data based on the number of participants meeting or exceeding predefined limits in terms of absolute QT / QTc intervals or changes from baseline will be presented. In addition, a listing of these participants will be produced by treatment group.All ECG data will be summarized by treatment and visit / time. Data regarding clinically significant ECG abnormalities will be provided by treatment and time point. Exploratory endpoint(s) / estimand(s) analysisPharmacokineticsOnly iptacopan Ctrough samples will be collected.Descriptive summary statistics of iptacopan plasma concentration data (i.e., Ctrough) will be provided by treatment and visit / sampling time point, including the frequency (n, %) of concentrations below the LLOQ and reported as zero in summary statistics; these will be distinguished from values missing.The PK analysis will include all participants in the data set with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement.Other planned analyses using pharmacokinetic data collected in this and potentially other studies would be specified in a separate Analysis plan (if conducted), describing principles and methods which will include population PK modeling. These analyses would be described in a separate report. BiomarkersSummary statistics and graphical summaries will be provided by visit and treatment group for urine and blood biomarkers. The number of values outside of the limits of quantification will be reported in each table. Values above ULOQ will be inputted as ULOQ in graphical summaries (with a special symbol) and for the calculation of the summary statistics. Values below the LLOQ will be inputted as LLOQ / 2 for these analyses. Interim analysisTwo interim analyses are planned during the study.The first interim analysis (IA1) is planned after approximately 40 patients reach Week 24. The second interim analysis (IA2) is planned after all patients (approximately 78) reach Week 24.For these participants the Week 24 and Week 48 data will be examined as a preliminary evaluation of proof of concept.Additional interim analyses may be conducted to support decision making concerning the current clinical study or in case of any safety concerns.Unblinded interim analysis results will be reviewed by the clinical team. The clinical team may communicate interim results (e.g. information needed for planning / modifying another study) to relevant  teams for information, consulting and / or decision purposes.Interim results may be used to prepare abstracts to scientific meetings. This would typically require Investigator input to abstract preparation. Every attempt will be made to assure that the Investigator will not have access to individual participants' data, but rather will review aggregate, summary data. Sample size determinationThe study is planning to enroll 78 participants (39 per arm). The sample size is based on feasibility given that AAV is a rare disease but still provides adequate power to test the null hypothesis for the primary endpoint as described below.Primary endpoint(s)Assuming there is no difference between arms in proportion of participants achieving sustained remission at Week 48 and a response rate of 70% in the control arm, a sample size of 39 patients per arm (including 10% drop-out rate) provides 71% power that the primary analysis will be statistically significant at the one-sided 10% significance level for the non-inferiority test with a 20% margin. The power increases to 75% if there is no drop-out or increases to 85% if the true difference for iptacopan vs SOC is 5%.The 20% non-inferiority margin is based on precedent in AAV trials (e.g. avacopan phase 2 and phase 3 trials) and considered appropriate for phase 2 trial in a rare disease setting with limited treatment options for patients.The control arm response rate is assumed to be approximately similar to the observed rates in the Phase 3 avacopan trial while considering stricter GC tapering during the induction. period.Table 12 indicates the sensitivity of power owing to the uncertainty around the assumptions for true treatment effect and control arm response rate. Table 12 Sensitivity of power to changes in assumptions for N=39 per arm True treatment difference for iptacopan vs SOC (%)Control arm response rate (%)Power1 for primary endpoint (1-sided 10% alpha and 20% NI margin)no dropouts (N=78)with 5% drop-out rate (N=74)with 10% drop-out rate (N=70)-56053.351.950.506070.769.067.356084.683.281.6-57056.054.553.007074.472.871.057088.387.085.51 Using Farrington-Manning score test for proportion difference. Expected OutcomeTable 13 Target criteria for regulatoryKey outcome Benefits: Effect sizeRisks: expected relative safety and / or identified risksEfficacy4 key benefits shown out of 6 total benefitsComplete RemissionComplete remission is a BVAS score of 0 and no use of glucocorticoids >5 mg at 24 wks for 4 wks; Base case (ref: Ava Ph3): remission at Wk26 = 72.%​ in avacopan group Upside case: remission at Wk24 >72%Sustained RemissionSustained remission is complete remission at Wk24 with no major relapse to Wk48Base case: sustained remission rate = 65.7% in avacopan groupUpside: >65.7% at Wk48Induction phase: Rapid  responseTime to reach BVAS of 0Base case: median = 90 days (ref: RTX renal vasculitis Ph3)​ in RTX group Upside: median <90 days​Induction and Maintenance phases: Renal functionBase case:  improvement of 5 mL / min / 1.73m2 at Wk48​ Upside (ref: Ava Ph3 in avacopan group = 7.3 at Wk52): >7.3 mL / min / 1.73 m2 at Wk48​ MCID for eGFR: 5 mL / min / 1.73m2 Currently, there is an unmet medical need for a safe and convenient treatment with rapid onset, reduction in steroid and immunosuppressant usage and a maintenance phase monotherapy, and decrease symptomology, preserve organ function and reduce mortality. Iptacopan will address this need and provides:Reduction of steroidsReduction in steroid and immunosuppressant usage and a maintenance phase monotherapy Reduce the potential for infections due to use of immunosuppressants including rituximabTime to remissionRapidly induce disease remission and sustain through maintenanceSymptomatologyPreserve organ function  EquivalentsThose skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims. References Bai X, Borrow R, Bukovski S, et al. (2019) Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe. J Infect; 79(6):528-541.Brad H. Rovin, Sharon G. Adler, Jonathan Barratt, Frank Bridoux, Kelly A. Burdge, Tak Mao Chan, H. Terence Cook, Fernando C. Fervenza, Keisha L. 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(2021) 2021 American College of Rheumatology / Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol; 73(8):1366-1383.Exley AR, Bacon PA, Luqmani RA, et al. (1997) Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum; 40(2):371-80.Furer V, Rondaan C, Heijstek MW, et al. (2020) 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis; 79(1):39-52.Gou SJ, Yuan J, Chen M, et al. (2013a) Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int; 83(1):129-37.Gou SJ, Yuan J, Wang C, et al. (2013b) Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN. Clin J Am Soc Nephrol; 8(11):1884-91.Goupil R, Brachemi S, Nadeau-Fredette AC, et al. (2013) Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis. Clin J Am Soc Nephrol; 8(3):416-23.Haut Conseil de la santé publique (HCSP)(2014) Avis: Actualisation de l’avis relatif à l’antibioprophylaxie et la vaccination méningococcique des personnes traitées par éculizumab (Soliris® 300 mg solution à diluer pour perfusion).Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. (2023) EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis; .Ispasanie E, Muri L, Schubart A, et al. (2021) Alternative Complement Pathway Inhibition Does Not Abrogate Meningococcal Killing by Serum of Vaccinated Individuals. Front Immunol; 12:747594.Jennette JC, Falk RJ, Bacon PA, et al. (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum; 65(1):1-11.King, et al. (2017) Avoidance of Harm From Treatment for ANCA-Associated Vasculitis. Curr Treatm Opt Rheumatol; 3(4):230-243.Kitching AR, Anders HJ, Basu N, et al. (2020) ANCA-associated vasculitis. Nat Rev Dis Primers; 6(1):71.Konar M, Granoff DM (2017) Eculizumab treatment and impaired opsonophagocytic killing of meningococci by whole blood from immunized adults. Blood; 130(7):891-899.Little MA, Nightingale P, Verburgh CA, et al. (2010) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis; 69(6):1036-43.McNamara LA, Topaz N, Wang X, et al. (2017) High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine. MMWR Morb Mortal Wkly Rep; 66(27):734-737.Miloslavsky EM, Naden RP, Bijlsma JW, et al. (2017) Development of a Glucocorticoid Toxicity Index (GTI) using multicriteria decision analysis. Ann Rheum Dis; 76(3):543-546.Mukhtyar C, Flossmann O, Hellmich B, et al. (2008) Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann Rheum Dis; 67(7):1004-10.Mukhtyar C, Lee R, Brown D, et al. (2009)Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis; 68(12):1827-32.Muri L, Ispasanie E, Schubart A, et al. (2021) Alternative Complement Pathway Inhibition Abrogates Pneumococcal Opsonophagocytosis in Vaccine-Naïve, but Not in Vaccinated Individuals. Front Immunol; 12:732146.Nguyen MTT, Lindegaard H, Hendricks O, et al. (2017) Initial Serological Response after Prime-boost Pneumococcal Vaccination in Rheumatoid Arthritis Patients: Results of a Randomized Controlled Trial. J Rheumatol; 44(12):1794-1803.Redondo-Rodriguez R, Mena-Vázquez N, Cabezas-Lucena AM, et al. (2022) Systematic Review and Metaanalysis of Worldwide Incidence and Prevalence of Antineutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis. J Clin Med; 11(9).Risitano AM, Röth A, Soret J, et al. (2021) Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol; 8(5):e344-e354.Robson J, Doll H, Suppiah R, et al. (2015) Glucocorticoid treatment and damage in the anti-neutrophil cytoplasm antibody-associated vasculitides: long-term data from the European Vasculitis Study Group trials. Rheumatology (Oxford); 54(3):471-81.Robson JC, Grayson PC, Ponte C, et al. (2022) 2022 American College of Rheumatology / European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis; 81(3):315-320.Sarnes E, Crofford L, Watson M, et al. (2011) Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther; 33(10):1413-32.Schubart A, Anderson K, Mainolfi N, et al. (2019) Small-molecule factor B inhibitor for the treatment of complement-mediated diseases. Proc Natl Acad Sci U S A; 116(16):7926-7931.Springer JM, Kermani TA, Sreih A, et al. (2020) Clinical Characteristics of an Internet-Based Cohort of Patient-Reported Diagnosis of Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Observational Study. J Med Internet Res; 22(7):e17231.Stone JH, McDowell PJ, Jayne DRW, et al. (2022) The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time. Semin Arthritis Rheum; 55:152010.Suppiah R, Robson JC, Grayson PC, et al. (2022) 2022 American College of Rheumatology / European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis. Ann Rheum Dis; 81(3):321-326.Thiel J, Rizzi M, Engesser M, et al. (2017) B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients. Arthritis Res Ther; 19(1):101.van Assen S, Agmon-Levin N, Elkayam O, et al. (2011) EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis; 70(3):414-22.Wade SD, Kyttaris VC (2021) Rituximab-associated hypogammaglobulinemia in autoimmune rheumatic diseases: a single-center retrospective cohort study. Rheumatol Int; 41(6):1115-1124.Xiao H, Schreiber A, Heeringa P, et al. (2007) Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol; 170(1):52-64. 

Claims

1. A method of treating ANCA-associated vasculitis (AAV) in a subject in need thereof comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of from about 50 mg to about 500 mg.

2. The method of claim 1, wherein the method comprises administering to the subject iptacopan hydrochloride.

3. The method of claim 1, wherein the method comprises administering to the subject iptacopan hydrochloride monohydrate.

4. The method of any one of claims 1 to 3, wherein the dose is from about 50 mg to about 250 mg.

5. The method of any one of claims 1 to 4, wherein the dose is from about 100 mg to about 200 mg.

6. The method of any one of claims 1 to 5, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.

7. The method of any one of claims 1 to 6, wherein the dose is about 50 mg.

8. The method of any one of claims 1 to 6, wherein the dose is about 100 mg.

9. The method of any one of claims 1 to 6, wherein the dose is about 200 mg.

10. The method of any one of the preceding claims, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

11. The method of any one of claims 1 to 10, wherein each dose is administered to the subject twice daily.

12. The method of any one of claims 1 to 11, wherein iptacopan or a pharmaceutically acceptable salt or hydrate thereof is administered orally.

13. The method of any one of claims 1 to 12, wherein the method further comprises administering to the subject at least one additional therapeutic agent selected from an immunosuppressant and / or rituximab.

14. The method of claim 13, wherein the at least one additional therapeutic agent comprises a non-steroidal immunosuppressant selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.

15. The method of claim 13, wherein the subject is administered a corticosteroid (or glucocorticoid).

16. The method of claim 15, wherein the corticosteroid is prednisone, prednisolone, triamcinolone, methylprednisolone, and / or dexamethasone.

17. The method of any one of claims 13 to 16, wherein the subject is administered rituximab.

18. The method of any one of the preceding claims, wherein the subject has been treated with at least one additional therapeutic agent prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

19. The method of claim 18, wherein the subject has received corticosteroid therapy prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

20. The method of any one of claims 18 to19, wherein the subject has a remission of AAV resulting from the prior administration of the at least one additional therapeutic agent, and wherein the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof maintains the remission or prevents relapse of AAV in the subject.

21. The method of claim 20, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).

22. The method of any one of claims 13 to 21, wherein the at least one additional therapeutic agent is administered to the subject concurrently with the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof during an induction period.

23. The method of claim 22, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

24. The method of claim 22 or 23, wherein the at least one additional therapeutic agent comprises rituximab, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and(2) about 1000 mg of rituximab intravenously at day 1 and week 2 from the start of the treatment, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1 from the start of the treatment.

25. The method of claim 22 or 23, wherein the at least one additional therapeutic agent comprises a glucocorticoid, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and(2) from about 40 mg / day to about 75 mg / day of the glucocorticoid, intravenously.

26. The method of claim 25, wherein the dose of the glucocorticoid is gradually reduced to ≤5 mg / day over a period of time following the induction period, optionally the period of time following the induction period is about 12 weeks to about 24 weeks.

27. The method of any one of claims 22 to 26, wherein the method further comprises, during a maintenance period post the induction period, the subject continuously receiving iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the same dose and frequency, alone or in combination with a reduced dose of glucocorticoid.

28. The method of claim 27, wherein the subject receives iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof at a dose of 200 mg twice daily during the maintenance period.

29. The method of claim 27 or 28, wherein during the maintenance period, the subject receives a glucocorticoid, orally at a dose of ≤5 mg daily.

30. The method of any one of claims 27 to 29, further comprising treating the subject with antibiotic prophylaxis during the maintenance period.

31. The method of any one of the preceding claims, wherein the subject has newly diagnosed or relapsed AAV.

32. The method of any one of the preceding claims, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA).

33. The method of any one of the preceding claims, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

34. The method of any one of the preceding claims, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide.

35. The method of any one of the preceding claims, wherein the subject is responsive to anti-PR3 or anti-MPO antibodies treatment.

36. The method of any one of the preceding claims, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

37. The method of any one of the preceding claims, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae.

38. The method of any one of the preceding claims, wherein the subject has a baseline level of circulating IgG of greater than 4.0 g / L.

39. The method of any one of the preceding claims, wherein the subject is an adult.

40. The method of any one of the preceding claims, wherein the subject exhibits a remission at week 24 from the start of the treatment.

41. The method of claim 40, wherein the subject exhibits a complete remission at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.

42. The method of claim 40 or 41, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).

43. The method of claim 41 or 42, wherein the complete remission is when the subject has a BVAS, e.g., BVASv3, score of 0 and no use of glucocorticoids at a dose of greater than 5 mg / day, at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.

44. The method of any one of claims 40 to 43, wherein the subject exhibits a sustained remission without major relapse until week 48, from the start of said treatment.

45. The method of any one of claims 40 to 44, wherein the subject exhibits a remission rate of greater than 72% at week 24 from the start of said treatment.

46. The method of any one of claims 40 to 44, wherein the subject exhibits a remission rate of greater than 65% at week 48 from the start of said treatment.

47. The method of any one of the preceding claims, wherein the subject exhibits a BVAS score of 0 within from about 80 days to about 100 days, after starting said treatment.

48. The method of any one of the preceding claims, wherein the subject exhibits an improved renal function, assessed by minimal clinically important difference (MCID) of Estimated Glomerular Filtration Rate (eGFR) over 48 weeks after starting said treatment.

49. A method for maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof, at dose of from about 50 mg to about 500 mg, wherein the subject has a remission of AAV resulting from a previous treatment.

50. The method of claim 49, wherein the dose is from about 50 mg to about 250 mg or from about 100 mg to about 200 mg.

51. The method of claim 49 or 50, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.

52. The method of any one of claims 49 to 51, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

53. The method of any one of claims 49 to 52, where the subject receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the dose orally twice daily.

54. The method of any one of claims 49 to 53, wherein the previous treatment comprises administering to the subject:1) iptacopan or a pharmaceutically acceptable salt or hydrate thereof;2) an immunosuppressant and / or rituximab; or 3) combination thereof.

55. The method of claim 54, wherein the immunosuppressant is selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.

56. The method of claim 54, wherein the immunosuppressant is a corticosteroid.

57. The method of any one of claims 54 to 56, wherein the previous treatment comprises a treatment with (1) iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, and (2) a corticosteroid and / or rituximab.

58. The method of any one of claims 49 to 57, wherein the subject receives about 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily.

59. The method of any one of claims 49 to 58, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day.

60. The method of any one of claims 49 to 59, wherein the remission of AAV is maintained for at least 4 weeks or at least 14 weeks.

61. The method of claim 60, wherein the remission of AAV is maintained for at least 24 weeks.

62. The method of any one of claims 49 to 61, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

63. A method for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, comprising:(1) administering to the subject during an induction period:iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily; wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment.

64. The method of claim 63, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

65. The method of claim 63 or 64, wherein the induction dose and the maintenance dose comprise the same amount of iptacopan or the pharmaceutically acceptable salt or hydrate thereof.

66. The method of any one of claims 63 to 65, wherein the induction dose and the maintenance dose comprises 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof, each administered orally twice daily.

67. The method of any one of claims 63 to 66, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

68. The method of any of claims 63 to 67, wherein the dosage of the steroid, non-steroidal immunosuppressant, and / or rituximab is gradually reduced or eliminated over a course from 12 weeks to 24 weeks, or about 16 weeks during the maintenance period.

69. The method of any one of claims 63 to 68, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and1000 mg of rituximab intravenously at day 1 and week 2, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1.

70. The method of any one of claims 63 to 68, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, andfrom about 40 mg / day to about 75 mg / day of a steroid, intravenously.

71. The method of any one of claims 63 to 70, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day during the maintenance period.

72. The method of claim 63, wherein the dosage of the non-steroidal immunosuppressant, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period.

73. The method of any one of claims 63 to 72, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

74. A method for reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises:administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose ranging from about 50 mg to about 500 mg twice daily, while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period.

75. The method of claim 74, comprising administering iptacopan or the pharmaceutically acceptable salt or hydrate thereof at a dose of about 200 mg orally twice daily during the initial treatment period and the subsequent treatment period.

76. The method of any one of claims 74 to 75, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

77. The method of claim 74 to 76, wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated over a course of about 12 weeks to 24 weeks, or about 16 weeks.

78. The method of any one of claims 74 to 77, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

79. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in a treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein the use comprises administering to the subject iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof at a dose of from about 50 mg to about 500 mg.

80. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 79, wherein the use comprises administering to the subject iptacopan hydrochloride.

81. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 79, wherein the use comprises administering to the subject iptacopan hydrochloride monohydrate.

82. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 81, wherein the dose is from about 50 mg to about 250 mg.

83. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 82, wherein the dose is from about 100 mg to about 200 mg.

84. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 82, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.

85. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 82, wherein the dose is about 50 mg.

86. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 82, wherein the dose is about 100 mg.

87. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 82, wherein the dose is about 200 mg.

88. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 87, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

89. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 88, wherein each dose is administered to the subject twice daily.

90. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 89, wherein iptacopan or a pharmaceutically acceptable salt or hydrate thereof is administered orally.

91. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 90, wherein the use further comprises administering to the subject at least one additional therapeutic agent selected from an immunosuppressant and / or rituximab.

92. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 91, wherein the at least one additional therapeutic agent comprises a non-steroidal immunosuppressant selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.

93. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 91, wherein the subject is administered a corticosteroid (or glucocorticoid).

94. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 93, wherein the corticosteroid is prednisone, prednisolone, triamcinolone, methylprednisolone, and / or dexamethasone.

95. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 91 to 94, wherein the subject is administered rituximab.

96. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 91 to 95, wherein the subject has been treated with at least one additional therapeutic agent prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

97. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 96, wherein the subject has received corticosteroid therapy prior to the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

98. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 97, wherein the subject has a remission of AAV resulting from the prior administration of the at least one additional therapeutic agent, and wherein the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof maintains the remission or prevents relapse of AAV in the subject.

99. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 98, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).

100. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 91 to 99, wherein the at least one additional therapeutic agent is administered to the subject concurrently with the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof during an induction period.

101. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 100, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

102. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 100 or 101, wherein the at least one additional therapeutic agent comprises rituximab, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and(2) about 1000 mg of rituximab intravenously at day 1 and week 2 from the start of the treatment, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1 from the start of the treatment.

103. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 100 or 101, wherein the at least one additional therapeutic agent comprises a glucocorticoid, and wherein during the induction period, the subject is administered:(1) about 200 mg of iptacopan or the pharmaceutically acceptable salt or hydrate thereof orally twice daily, and(2) from about 40 mg / day to about 75 mg / day of the glucocorticoid, intravenously.

104. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 103, wherein the dose of the glucocorticoid is gradually reduced to ≤5 mg / day over a period of time following the induction period, optionally the period of time is about 12 weeks to about 24 weeks.

105. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 100 to 104, wherein the use further comprises, during a maintenance period post the induction period, the subject continuously receiving iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the same dose and frequency, alone or in combination with a reduced dose of glucocorticoid.

106. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 105, wherein the subject receives iptacopan or the pharmaceutically acceptable salt or hydrate thereof at a dose of 200 mg twice daily during the maintenance period.

107. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 105 or 106, wherein during the maintenance period, the subject receives a glucocorticoid, orally at a dose of ≤5 mg daily.

108. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 105 to 107, further comprising treating the subject with antibiotic prophylaxis during the maintenance period.

109. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 108, wherein the subject has newly diagnosed or relapsed AAV.

110. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 109, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA).

111. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 110, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

112. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 111, wherein the subject has newly diagnosed or relapsed granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) that requires treatment with rituximab and / or cyclophosphamide.

113. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 112, wherein the subject is responsive to anti-PR3 or anti-MPO antibodies treatment.

114. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 113, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against one or more of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

115. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 114, wherein the subject has been vaccinated prior to administration of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof against Neisseria meningitidis, Streptococcus pneumoniae, and / or Haemophilus influenzae.

116. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 115, wherein the subject has a baseline level of circulating IgG of greater than 4.0 g / L.

117. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 116, wherein the subject is an adult.

118. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 117, wherein the subject exhibits a remission at week 24 from the start of the treatment.

119. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 118, wherein the subject exhibits a complete remission at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.

120. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 118 or 119, wherein the remission status of the subject is evaluated using Birmingham Vasculitis Activity Score (BVAS), in particular Birmingham Vasculitis Activity Score Version 3.0 (BVASv3).

121. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 120, wherein the complete remission is when the subject has a BVAS, e.g., BVASv3, score of 0 and no use of glucocorticoids at a dose of greater than 5 mg / day, at week 24 from the start of the treatment, and wherein the complete remission is maintained for at least 4 weeks.

122. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 118 to 121, wherein the subject exhibits a sustained remission without major relapse until week 48, from the start of said treatment.

123. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 118 to 122, wherein the subject exhibits a remission rate of greater than 72% at week 24 from the start of said treatment.

124. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 118 to 122, wherein the subject exhibits a remission rate of greater than 65% at week 48 from the start of said treatment.

125. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 124, wherein the subject exhibits a BVAS score of 0 within from about 80 days to about 100 days, after starting said treatment.

126. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 79 to 125, wherein the subject exhibits an improved renal function, assessed by minimal clinically important difference (MCID) of Estimated Glomerular Filtration Rate (eGFR) over 48 weeks after starting said treatment.

127. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in maintaining the remission of ANCA-associated vasculitis (AAV) or preventing relapse of AAV in a subject in need thereof, comprising administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof, at dose of from about 50 mg to about 500 mg, wherein the subject has a remission of AAV resulting from a previous treatment.

128. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 127, wherein the dose is from about 50 mg to about 250 mg or from about 100 mg to about 200 mg.

129. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 127, wherein the dose is about 50 mg, about 75 mg, about 100 mg, about 150 mg, or about 200 mg.

130. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 127 to 129, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

131. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 127 to 130, where the subject receives iptacopan or a pharmaceutically acceptable salt or hydrate thereof at the dose orally twice daily.

132. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 127 to 131, wherein the previous treatment comprises administering to the subject:1) iptacopan or a pharmaceutically acceptable salt or hydrate thereof;2) an immunosuppressant and / or rituximab; or 3) combination thereof.

133. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 132, wherein the immunosuppressant is selected from the group consisting of mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, and cyclophosphamide.

134. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 132, wherein the immunosuppressant is a corticosteroid.

135. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 132, wherein the previous treatment comprises a treatment with (1) iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, and (2) a corticosteroid and / or rituximab.

136. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 127 to 135, wherein the subject receives about 200 mg of iptacopan orally twice daily.

137. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 127 to 136, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day.

138. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use any one of claims 127 to 137, wherein the remission of AAV is maintained for at least 4 weeks or at least 14 weeks.

139. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use claim 138, wherein the remission of AAV is maintained for at least 24 weeks.

140. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use any one of claims 127 to 139, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

141. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, comprising:(1) administering to the subject during an induction period:iptacopan or a pharmaceutically acceptable salt or hydrate thereof at an induction dose ranging from about 50 mg to about 500 mg twice daily; and at least one background therapeutic agent selected from the group consisting of a non-steroidal immunosuppressant, a steroid, and rituximab; and (2) administering to the subject during a maintenance period post the induction period: iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a maintenance dose ranging from about 50 mg to about 500 mg twice daily;wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated during the treatment.

142. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 141, wherein the induction period lasts for 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 14, weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, or 24 weeks after initiation of the administration of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

143. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 141 or 142, wherein the induction dose and the maintenance dose comprise the same amount of iptacopan or the pharmaceutically acceptable salt or hydrate thereof.

144. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 143, wherein the induction dose and the maintenance dose comprises 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof, each administered orally twice daily.

145. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 144, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

146. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any of claims 141 to 145, wherein the dosage of the steroid, non-steroidal immunosuppressant, and / or rituximab is gradually reduced or eliminated over a course from 12 weeks to 24 weeks, or about 16 weeks during the maintenance period.

147. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 146, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, and1000 mg of rituximab intravenously at day 1 and week 2, or 375 mg / m2 of rituximab intravenously weekly for four weeks starting from day 1.

148. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 146, comprising administering to the subject, during the induction treatment period: 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof orally twice daily, andfrom about 40 mg / day to about 75 mg / day of a steroid, intravenously.

149. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 148, wherein the subject further receives corticosteroid at a dose of ≤5 mg / day during the maintenance period.

150. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 149, wherein the dosage of the non-steroidal immunosuppressant, a steroid, and rituximab is reduced or eliminated at the end of the induction treatment period.

151. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 141 to 150, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

152. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use in reducing a dependence of a subject in need thereof on a background treatment with a steroid, cyclophosphamide, and / or rituximab, wherein the subject has AAV that is controlled, partially controlled, or uncontrolled with the background treatment, wherein the method comprises:administering to the subject iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose ranging from about 50 mg to about 500 mg twice daily, while maintaining the background treatment during an initial treatment period; and gradually reducing or eliminating the dosage of the steroid, cyclophosphamide, and / or rituximab administered to the subject over a course of a subsequent treatment period while continuing administering iptacopan or a pharmaceutically acceptable salt or hydrate thereof to the subject at the same dose and frequency used during the initial treatment period.

153. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 152, comprising administering iptacopan or a pharmaceutically acceptable salt or hydrate thereof at a dose of about 200 mg orally twice daily during the initial treatment period and the subsequent treatment period.

154. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 152 to 153, wherein the dosing amount refers to the anhydrous free base of iptacopan hydrochloride.

155. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of claim 152 to 154, wherein the dosage of the steroid, cyclophosphamide, and / or rituximab is gradually reduced or eliminated over a course of about 12 weeks to 24 weeks, or about 16 weeks.

156. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for use of any one of claims 152 to 155, wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA) and / or eosinophilic granulomatosis with polyangiitis (EGPA), e.g., wherein the subject has granulomatosis with polyangiitis (GPA) and / or microscopic polyangiitis (MPA).

157. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for treating ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.

158. Iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof for treating ANCA-associated vasculitis (AAV) in a subject in need thereof in accordance to any one of the preceding claims, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.

159. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of any one of claims 79 or 158, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for oral administration.

160. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of claim 159, wherein the iptacopan or a pharmaceutically acceptable salt thereof is contained in a capsule.

161. The iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof of claim 160, wherein the capsule comprises 200 mg of iptacopan or a pharmaceutically acceptable salt or hydrate thereof.

162. A pharmaceutical composition comprising iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof and at least one pharmaceutically acceptable carrier for use in treating ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein the iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.

163. The pharmaceutical composition of claim 162, which comprises 200 mg of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof.

164. The pharmaceutical composition of claim 162 or 163 for use in accordance with any one of the preceding claims.

165. Use of iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof in the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is administered to the subject at a dose of from about 50 mg to about 500 mg.

166. Use of in the manufacture of a medicament for the treatment of ANCA-associated vasculitis (AAV) in a subject in need thereof, wherein iptacopan or a pharmaceutically acceptable salt thereof or hydrate thereof is formulated for administration to the subject at a dose of from about 50 mg to about 500 mg.

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