Methods of using interleukin-23 receptor antagonists

Abstract

The present invention relates to methods of administering a cyclic peptide inhibitor of the interleukin-23 receptor (IL-23R) or pharmaceutically acceptable salt or solvate forms thereof, corresponding compositions, methods, and / or uses for treatment of psoriatic arthritis.

Description

[0001]

[0002] METHODS OF USING INTERLEUKIN-23 RECEPTOR ANTAGONISTS

[0003] FIELD

[0004] The present invention relates to methods of administering a peptide inhibitor of the interleukin-23 receptor (IL-23R), or a pharmaceutically acceptable salt or solvate form thereof, and other corresponding assays, methods and / or uses for treatment of psoriatic arthritis. BACKGROUND

[0005] IL-23 is a heterodimer composed of a unique p 19 subunit and the p40 subunit shared with IL- 12, which is a cytokine involved in the development of interferon-y (IFN-y)-producing T helper 1 (TRI) cells. Although IL-23 and IL-12 both contain the p40 subunit, they have different phenotypic properties. For example, animals that are deficient in IL- 12 are susceptible to inflammatory autoimmune diseases, whereas IL-23 deficient animals are resistant to such diseases, presumably due to a reduced number of CD4+T cells producing IL-6, IL- 17, and TNF in the CNS of IL-23-deficient animals. IL-23 binds to IL-23R. Binding of IL-23 to IL-23R activates the Jak-Stat signaling molecules, Jak2, Tyk2, and Statl, Stat 3, Stat 4, and Stat 5, although Stat 4 activation is substantially weaker. In addition, different DNA-binding Stat complexes form in response to IL-23 as compared with IL- 12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with Stat 3. In contrast to IL-12, which acts mainly on naive CD4(+) T cells, IL-23 preferentially acts on memory CD4(+) T cells.

[0006] Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral and axial joints that affects approximately 0.02% to 0.25% of the general population. Psoriatic arthritis is a multi-faceted disease that impacts the joints, soft tissues, and skin, all of which affect quality of life. The burden of disease can be severe, with some patients developing destructive arthritis leading to bone erosions and loss of joint structure; some patients require surgical intervention to alleviate pain and restore function of severely damaged joints. There is a need for an effective treatment, specifically oral treatment, for psoriatic arthritis patients.

[0007] SUMMARY

[0008] The present invention addresses these needs by providing peptide inhibitors or pharmaceutically acceptable salt or solvate forms thereof which are suitable for oral administration that bind IL-23R to inhibit IL-23 binding and signaling. Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising administering an IL-23 receptor antagonist peptide, wherein after treating with the IL-23 receptor antagonist peptide, the subject is a responder to treatment by at least one measure of response to treatment selected from the group consisting of a 20% improvement in the American College of Rheumatology core set disease index (ACR20) a 50% improvement in the American College of Rheumatology core set disease index (ACR50). a 70% improvement in the American College of Rheumatology core set disease index (ACR70), Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C-reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and vdH-S score.

[0009] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising administering a compound of Formula (I): a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof; wherein after treating with the IL-23 receptor antagonist peptide, the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment..

[0010] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising administering a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof; wherein after treating with the IL-23 receptor antagonist peptide, the subject achieves a psoriatic arthritis measure of response determined by at least one criteria selected from the group consisting of a 20% improvement in the American College of Rheumatology core set disease index (ACR20), a 50% improvement in the American College of Rheumatology core set disease index (ACR50). a 70% improvement in the American College of Rheumatology core set disease index (ACR70), Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C-reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). or vdH-S score.

[0011] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof; wherein after treating with the IL- 23 receptor antagonist peptide, the subject achieves Arc 20 and further achieves an improvement in a disease activity determined by at least one criteria selected from the group consisting of (i) improvement in disease activity as determined by the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75 / 90 / 100), (ii) an Investigator's Global Assessment (IGA) Score of 0 / 1 and >2 grades improvement from baseline (among participants with baseline body surface area (BSA) >3% and with baseline IGA score >2), (iii) improvement in disease activity as determined by the

[0012] American College of Rheumatology 50% and 70% improvement criteria (ACR50 / 70), (iv) change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), and (v) change from baseline in SF-36 physical component summary (PCS).

[0013] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering to the subject about 200 mg of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the subject is a human diagnosed with psoriatic arthritis.

[0014] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering to the subject about 400 mg of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the subject is a human diagnosed with psoriatic arthritis.

[0015] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a hydrochloride salt of the compound of Formula (I) to a patient in need thereof in an amount of about 200 mg, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

[0016] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a hydrochloride salt of the compound of Formula (I)

[0017] to a patient in need thereof in an amount of about 400 mg, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment. In some embodiments, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is a hydrochloride salt of the compound of Formula (I) or solvate thereof. In some embodiments, the treatment comprises orally administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof. In some embodiments, the treatment comprises administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof daily.

[0018] In some embodiments, the present invention relates to a method and / or use for treating psoriatic arthritis, which comprises administering a composition that includes:

[0019] (a) a compound of Formula (I):

[0020] a pharmaceutically acceptable salt or solvate thereof; and

[0021] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof.

[0022] BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 shows an XRPD pattern of a crystalline form of a hydrochloride salt of a compound of Formula (I).

[0024] DETAILED DESCRIPTION

[0025] The invention herein, provides an effective treatment of psoriatic arthritis using an oral IL-23 receptor antagonist. The IL-23 receptor antagonist, as described below and supported by clinical trial studies, provides a new and effective therapy for psoriatic arthritis patients, with both superior efficacy, ease of administration, improved patient adherence, low anti-drug antibody (ADA) risk, and a better safety profile.

[0026] “A,” “an,” or “a(n)”, is an indefinite article when used in reference to a group of substituents or “substituent group” herein, mean at least one.

[0027] “About” when referring to a value includes the stated value + / - 10% of the stated value. For example, about 50% includes a range of from 45% to 55%, while about 20 molar equivalents includes a range of from 18 to 22 molar equivalents. Accordingly, when referring to a range, “about” refers to each of the stated values + / - 10% of the stated value of each end of the range. For instance, a ratio of from about 1 to about 3 (weight / weight) includes a range of from 0.9 to

[0028] 3.3.

[0029] “Administering” refers to administration of the composition of the present invention to a subject.

[0030] “Composition” or “pharmaceutical composition” as used herein is intended to encompass a product that includes the specified active product ingredient (API) (i.e., as defined in the instant specification as a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof) and pharmaceutically acceptable excipients, carriers or diluents as described herein, which results from combination of specific components.

[0031] An “empty stomach” or “fasted” state refers to abstaining from food intake for at least 2 hours before administration of the composition of the present invention and abstaining from food and liquid intake for at least 30 minutes after administration of the composition of the present invention.

[0032] A “PASI score” refers to a numerical value resulting from evaluation using the Psoriasis Area and Severity Index (PASI). PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy.

[0033] As used herein, a “PASI xx response” indicates a greater than or equal to xx% reduction in Psoriasis Area and Severity Index (PASI) score after treatment as compared to before treatment. In an illustrative example, a PASI 50 response in a subject treated with the composition of the present invention is a subject that has a greater than or equal to 50% reduction in PASI score after treatment. Hence, a subject having a PASI 72 score before treatment and having a PASI 36 score or lower after treatment is said to achieve a PASI 50 response.

[0034] “Patient” or “subject” refers to a living organism, which includes, but is not limited to a human subject suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Further non-limiting examples may include, but are not limited to, humans or other mammals. In some embodiments, the subject is a human.

[0035] “Pharmaceutically acceptable excipient” includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals or as conventionally understood in or by skilled artisans who work in the formulary arts.

[0036] Pharmaceutically acceptable salts of the compounds of the present invention are salts formed with acids, such as of mineral acids, organic carboxylic and organic sulfonic acids, hydrochloric acid, methanesulfonic acid, maleic acid, are also possible provided a basic group, such as an amine, constitutes part of the structure.

[0037] “Salt” as used herein refers to acid or base salts of the compounds used in the methods of the present invention. Illustrative examples of pharmaceutically acceptable salts are mineral acid (hydrochloric acid, hydrobromic acid, phosphoric acid, and the like) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid and the like) salts, quaternary ammonium (methyl iodide, ethyl iodide, and the like) salts. It is understood that the pharmaceutically acceptable salts are non-toxic.

[0038] The compounds of the invention may form solvates, for example with water (i.e. hydrates) or common organic solvents. As used herein, the term “solvate” means a physical association of the compounds of the present invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. The term “solvate” is intended to encompass both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include compounds of the invention in combination with water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid or ethanolamine and the like. The compounds of the invention may exert their biological effects when they are in solution. Solvates are well known in the pharmaceutical industry. They can be important to the process for the preparation of a substance (e.g. in relation to their purification, the storage of the substance (e.g. its stability) and the ease of handling the substance and are often formed as part of the isolation or purification stages of a chemical synthesis. A person skilled in the art can determine whether a hydrate or other solvate has formed by the isolation conditions or purification conditions used to prepare a given compound using techniques such as thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray crystallography (e.g. single X-ray crystallography or X-ray powder diffraction) and Solid-State NMR (SS-NMR also known as Magic Angle Spinning NMR or MAS-NMR).

[0039] “Therapeutically effective amount” refers to an amount of a compound or of a pharmaceutical composition useful for treating or ameliorating an identified disease or condition, or for exhibiting a detectable therapeutic or inhibitory effect. "Therapeutically effective amount" further includes within its meaning a non-toxic but sufficient amount of the particular drug to which it is referring to provide the desired therapeutic effect. The exact amount required will vary from subject to subject depending on factors such as the patient's general health, the patient's age, etc. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003. Gennaro, Ed., Lippincott, Williams & Wilkins).

[0040] “Safe and effective amount" as used herein in the context of a dose, dosage regimen, treatment or method refer to the effectiveness of a particular dose, dosage, or treatment regimen. Efficacy can be measured based on change in the course of the disease in response to an agent of the present invention. For example, the IL-23 receptor antagonist of the present invention (e.g., the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof) is administered to a subject in an amount and for a time sufficient to induce an improvement, preferably a sustained improvement, in at least one indicator that reflects the severity of the disorder that is being treated. Various indicators that reflect the extent of the subject's illness, disease or condition can be assessed for determining whether the amount and time of the treatment is sufficient. Such indicators include, for example, clinically recognized indicators of disease severity, symptoms, or manifestations of the disorder in question. The degree of improvement generally is determined by a physician, who can make this determination based on signs, symptoms, biopsies, or other test results, and who can also employ questionnaires that are administered to the subject, such as quality-of-life questionnaires developed for a given disease. For example, an IL-23 receptor antagonist of the present invention can be administered to achieve an improvement in a subject’s condition related to psoriatic arthritis.

[0041] Improvement can be indicated by an improvement in an index of disease activity, by amelioration of clinical symptoms or by any other measure of disease activity. Once such index of disease is the American College of Rheumatology core set disease index (ARC 20), ARC

[0042] (50), ARC (70). Other index can include Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C- reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PAS I), Dermatology Life Quality Index (DLQI), Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and vdH-S score.

[0043] The term “clinically safe,” as it relates to a dose, dosage regimen, treatment or method with IL-23 receptor antagonist of the present invention (e.g., the compound of formula I or a pharmaceutically acceptable salt or solvate thereof), refers to a favorable risk:benefit ratio with an acceptable frequency and / or acceptable severity of treatment-emergent adverse events (referred to as AEs or TEAEs) compared to the standard of care or to another comparator. As used herein, “adverse event,” “treatment-emergent adverse event,” and “adverse reaction” mean any harm, unfavorable, unintended or undesired sign or outcome associated with or caused by administration of a pharmaceutical composition or therapeutic. It is an untoward medical occurrence in a subject administered a medicinal product. However, abnormal values or observations are not reported as adverse events unless considered clinically significant by the investigator. As used herein, when referring to an adverse event, “clinically apparent” means clinically significant as determined by a medical doctor or an investigator using standard acceptable to those of ordinary skill in the art. When the harm or undesired outcome of adverse events reaches such a level of severity, a regulatory agency can deem the pharmaceutical composition or therapeutic unacceptable for the proposed use. In particular, “safe” as it relates to a dose, dosage regimen or treatment with IL-23 receptor antagonist of the present invention refers to with an acceptable frequency and / or acceptable severity of adverse events associated with treatment if attribution is considered to be possible, probable, or very likely due to the use of the IL-23 receptor antagonist.

[0044] “Treat”, “treating” and “treatment” refer to any indicia of success in the treatment or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient's physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and / or a psychiatric evaluation.

[0045] The term, “pharmaceutical product” is product that contains an active pharmaceutical ingredient that has shown to be a safe and effective treatment of one or more indications as supported by findings from clinical trials regulated by a governmental authority, e.g., the Food and Drug Administration or the similar authority in other countries.

[0046] The term, “subject” or “subjects” refers to a human patient. Examples of human patient include but are not limited to an adult (> 18 years old) human patient and adolescent (> 12 years old and < 18 years old) human patient.

[0047] In describing the present invention, abbreviations and symbols utilized herein are in accordance with the common usage of such abbreviations and symbols by those skilled in the chemical and biological arts. Specifically, the following abbreviations may be used in the examples and throughout the specification:

[0048] List of Standard Chemical Definitions

[0049] COMPOUND

[0050] The present invention relates to a IL-23 receptor antagonist useful for treating psoriatic arthritis. In some embodiments, the IL-23 receptor antagonist is a peptide. In some embodiments, the IL-23 receptor antagonist is a cyclic peptide.

[0051] The present invention relates to a compound of Formula (I), Ac-[Pen]*-N-T-[W(7-Me)]- [Lys(Ac)]-[Pen]*-Phe[4-(2-aminoethoxy)]-[2-Nal]-[THP]-E-N-[3-Pal]-Sarc-NH2(* [Pen] -[Pen]* form disulfide bond): a pharmaceutically acceptable salt or solvate form thereof. The compound of formula (I) has an amino acid string of Ac-[Pen]*-N-T-[W(7-Me)]-[Lys(Ac)]-[Pen]*-Phe[4-(2- aminoethoxy)]-[2-Nal]-[THP]-E-N-[3-Pal]-Sarc-NH2 (* [Pen] -[Pen]* form disulfide bond), wherein all amino acid residues are all in L forms.

[0052] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof may be present in any form, such as a pharmaceutically acceptable salt, hydrate, or other solvate. In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof may be provided in crystalline form, in an amorphous form, or a semi-crystalline form.

[0053] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is a salt. In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is an acetate salt. In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is a bis-acetate salt. In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is an acetate. In some embodiments, the acetate of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is an amorphous form. In some embodiments, the acetate of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is the acetate salt. In some embodiments, the acetate of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is the bis-acetate salt. In some embodiments, the acetate salt of the composition of the present invention is an amorphous form. In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is a solvate. In some embodiments, the acetate form of the compound of Formula (I) is the acetate solvate.

[0054] The present invention also provides a crystalline form of a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a solvate of the foregoing. The pharmaceutically acceptable salts of a compound of formula (I) provided herein include hydrochloride salts, bishydrochloride salts, acetate salts, fumarate salts, glutarate salts, glycolate salts, mesylate salts, sulfate salts, and citrate salts.

[0055] The present invention also provides a crystalline form of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a solvate of the foregoing. The pharmaceutically acceptable salts of the compound of Formula (I) provided herein include hydrochloride salt, bis- hydrochloride salt, acetate salt, fumarate salt, glutarate salt, glycolate salt, mesylate salt, sulfate salt, and citrate salt.

[0056] In particular, the present invention provides a crystalline hydrochloride salt form of a compound of Formula (I) that has the structure:

[0057] In some embodiments, the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof is a hydrochloride salt of the compound of Formula (I) or solvate thereof.

[0058] In some embodiments, the compound of formula (I) or pharmaceutically acceptable salt thereof is a hydrochloride salt form of the compound of formula (I). In some embodiments, the compound of formula (I) or pharmaceutically acceptable salt thereof is a hydrochloride salt form of the compound of formula (I) characterized by an XRPD pattern substantially as set forth in FIG. 22.

[0059] In some embodiments, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is crystalline and in the form of a solvate. In some embodiments, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is crystalline and in the form of a salt.

[0060] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.2, 6.9, 7.6, and 9.2 + / - 0.2 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.2, 6.9, 7.6, and 9.2 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.2, 6.9, 7.6, and 9.2 + / - 0.4 degrees two theta.

[0061] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 10.0, 10.7, 12.2, 13.9, 15.7, or 17.1 + / - 0.2 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 10.0,

[0062] 10.7, 12.2, 13.9, 15.8, or 17.1 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 10.0, 10.7, 12.2, 10.0, 10.7, 12.1, 13.9, 15.8, or 17.1 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.2, 10.0, 10.7, 12.1, 13.9, 15.8, or 17.1 + / - 0.4 degrees two theta.

[0063] In other embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1, 13.3, 14.0, 14.8, 15.8, 17.1. 17.6. 18.1. 18.6. 19.3. 20.5, 20.7, or 21.8 + / - 0.2 degrees two theta. In other embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1, 13.3, 14.0, 14.8,

[0064] 15.8, 17.1, 17.6, 18.1, 18.6, 19.3, 20.5, 20.7, or 21.8 + / - 0.3 degrees two theta. In other embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1 , 13.3, 14.0, 14.8, 15.8, 17.1, 17.6, 18.1, 18.6, 19.3, 20.5, 20.7, or 21.8 + / - 0.4 degrees two theta.

[0065] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1, 13.3, 14.0, 14.8, 15.8,

[0066] 17.1, 17.6, 18.1, 18.6, 19.3. 20.5. 20.7. or 21.8 + / - 0.2 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least

[0067] 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1, 13.3, 14.0, 14.8, 15.8, 17.1, 17.6, 18.1, 18.6,

[0068] 19.3, 20.5, 20.7, or 21.8 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least 4.3, 6.9, 7.7, 8.6, 9.3, 10.0, 10.7, 11.5, 12.0, 13.1, 13.3, 14.0, 14.8, 15.8, 17.1, 17.6, 18.1, 18.6, 19.3, 20.5, 20.7, or 21.8 + / - 0.4 degrees two theta.

[0069] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 9.4, 10.0, 10.8, 11.5, 12.0,

[0070] 12.2, 12.8, 13.1, 13.3, 13.8, 13.9, 14.2, 14.4, 14.7, 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7,

[0071] 19.2, 19.6, 19.9, 20.5, and 20.8 + / - 0.2 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2,

[0072] 6.9, 7.6, 8.5, 9.3. 9.4, 10.0, 10.8, 11.6, 12.0, 12.2, 12.8. 13.1. 13.3. 13.8, 13.9, 14.2, 14.4, 14.7,

[0073] 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7, 19.2, 19.6, 19.9, 20.5, and 20.8 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having two or more diffraction peaks at two theta angles selected from 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 9.4, 10.0, 10.8, 11.5, 12.0, 12.2, 12.8, 13.1, 13.3, 13.8, 13.9, 14.2, 14.4, 14.7, 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7, 19.2, 19.6,

[0074] 19.9, 20.5, and 20.8 + / - 0.4 degrees two theta.

[0075] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 9.4, 10.0, 10.8, 11.5, 12.0, 12.2, 12.8, 13.1,

[0076] 13.3, 13.8, 13.9, 14.2, 14.4, 14.7, 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7, 19.2, 19.6, 19.9,

[0077] 20.5, and 20.8 + / - 0.2 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 9.4, 10.0, 10.8,

[0078] 11.5, 12.0, 12.2, 12.8, 13.1, 13.3, 13.8, 13.9, 14.2, 14.4, 14.7, 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7, 19.2, 19.6, 19.9. 20.5. and 20.8 + / - 0.3 degrees two theta. In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having an XRPD pattern having diffraction peaks at two theta angles of at least 3.8, 4.2, 6.9, 7.6, 8.5, 9.3, 9.4, 10.0, 10.8, 11.5, 12.0, 12.2, 12.8, 13.1, 13.3, 13.8, 13.9, 14.2, 14.4, 14.7, 15.3, 15.7, 16.2, 16.4, 17.2, 17.6, 18.2, 18.7, 19.2, 19.6, 19.9, 20.5, and 20.8 + / - 0.4 degrees two theta.

[0079] In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having endotherm peaks at about 81.4 °C, as determined by differential scanning calorimetry (DSC). In some embodiments, the crystalline hydrochloride salt of the compound of Formula (I) or solvate thereof is characterized as having a weight loss of about 5.6% from about 26.5 °C to about 160.0 °C, as determined by thermogravimetric analysis (TGA).

[0080] In one aspect, the hydrochloride salt of a compound of Formula (I) or solvate thereof is a hemi hydrochloride salt. In some embodiments, the hemi hydrochloride salt has from about 0.1 to about 0.9, such as from about 0.2 to about 0.8 or from about 0.3 to about 0.7, molar equivalents of hydrogen chloride compared to the compound of Formula (I). In some embodiments, the hemi hydrochloride salt has about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, or about 0.9 molar equivalents of hydrogen chloride compared to the compound of Formula (I). In some embodiments, the hemi hydrochloride salt has about 0.5 molar equivalents of hydrogen chloride compared to the compound of Formula (I).

[0081] In some embodiments, the molar equivalents of a chloride anion of a crystalline hydrochloride salt of a compound of Formula (I) relative to one mole of the compound of Formula (I) is from about 0.2 to about 2.0. In some embodiments, the molar equivalents of a chloride anion of a crystalline hydrochloride salt of a compound of Formula (I) relative to one mole of the compound of Formula (I) is from about 0.4 to about 1.5. In other embodiments, the molar equivalents of a chloride anion of a crystalline hydrochloride salt of a compound of Formula (I) relative to one mole of the compound of Formula (I) is from about 0.5 to about 1.0.

[0082] In certain embodiments, the molar equivalents of a chloride anion of a crystalline hydrochloride salt of the compound of Formula (I) relative to one mole of the compound of Formula (I) is from about 0.6 to about 0.7.

[0083] In some embodiments, the hydrochloride salt of a compound of Formula (I) or solvate thereof may be a hydrate. In some embodiments, the hydrate of the hydrochloride salt of a compound of Formula (I) has from about 0.2 to about 10 molar equivalents of water compared to the compound of Formula (I).

[0084] Alternatively, the skilled person can deliberately form a solvate using crystallization conditions that include an amount of the solvent required for the particular solvate. Thereafter the methods described above, can be used to establish whether solvates had formed.

[0085] COMPOSITIONS

[0086] The present invention also relates to compositions of a compound of Formula (I). Suitable compositions of the present invention may be in different forms, including, but are not limited to a liquid composition, such as a solution composition, or a tablet composition. When the composition is a tablet, the tablet can include two or more different phases, including an internal phase and an external phase that can contain a core. The tablet composition can also include one or more coatings.

[0087] Compositions intended for oral use may contain one or more excipients including sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a palatable preparation. Tablets containing the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients which are suitable for manufacture of tablets are acceptable. These excipients may be, for example, inert diluents, such as calcium or sodium carbonate, lactose, lactose monohydrate, croscarmellose sodium, povidone, calcium or sodium phosphate; granulating and disintegrating agents, such as maize starch, or alginic acid; binding agents, such as cellulose, microcrystalline cellulose, starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc.

[0088] In some embodiments, the composition comprises the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof in an amount of about 5 mg to about 600 mg; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition comprises the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof in an amount of about 5 mg to about 400 mg; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition comprises the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof in an amount of about 5 mg to about 200 mg; and one or more pharmaceutically acceptable excipients.

[0089] In some embodiments, the composition includes 200 mg of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate form thereof; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition includes 400 mg of a compound of Formula (I), or a pharmaceutically acceptable salt or solvate form thereof; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition is a tablet. In some embodiments, the tablet is film coated. In some embodiments, the tablet is an immediate- release tablet. In some embodiments, the tablet is an immediate-release film-coated tablet. In some embodiments, the composition is a solution.

[0090] In some embodiments, the composition is an oral immediate-release film-coated tablet containing 200 mg of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition is an oral immediate-release film-coated tablet containing 400 mg of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof; and one or more pharmaceutically acceptable excipients. In some embodiments, the composition is a tablet. In some embodiments, the tablet is film coated. In some embodiments, the tablet is an immediate-release tablet. In some embodiments, the tablet is an immediate -release film-coated tablet. In some embodiments, the composition is a solution.

[0091] The compound of Formula (I) is prepared in film-coated tablets supplied in a 200 mg strength for oral administration. In some embodiments, each tablet contains a hydrochloride salt of the compound of Formula (I), with an amount of the compound of Formula (I) equivalent to 200 mg and the following ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, and silicified microcrystalline cellulose. The tablet coating contains the following inactive ingredients: glyceryl monocaprylocaprate, iron oxide yellow, macrogol polyvinyl alcohol graft polymer, polyvinyl alcohol partially hydrolyzed, talc, titanium dioxide.

[0092] In some embodiments, the composition comprises about 20% Compound of Formula (I) , about 0.4% of colloidal anhydrous silica, about 74.1% of silicified microcrystalline cellulose, about 5.0 % crospovidone, and about 0.5% magnisum sterate (all percentage by weight). In some embodiments, the amount of the compound of formula (I) in the pharmaceutical composition is about 200 mg. The method of claims 29, wherein the pharmaceutical composition further comprises about 30 mg coating. In some embodiments, the pharmaceutical composition further comprises about 3% (w / w%) coating. In some embodiments, the coating is Opadry QX 321A220063 Yellow Coating. In some embodiments, the pharmaceutical composition is in a tablet form.

[0093] In some embodiments, the composition is an immediate release, oval shaped, film- coated (FC) tablet for oral administration, containing a hydrochloride salt of the compound of Formula (I) having equivalent to 200 mg the compound of formula (I). In some embodiments, the tablet is a yellowish orange to yellowish brown film coated tablet of approximately 19 mm length. Table i and Table ii below show the composition of the tablet.

[0094] Table i: Composition of the 200mg film coated Tablet

[0095] Table ii. Composition of Opadry® QX 321A220063 Yellow Coating Powder

[0096] METHODS OF ADMINISTRATION, TREATMENT, AND / OR USES

[0097] In some embodiments, the present invention relates to a method and / or use for administering to the subject a composition disclosed herein. In some embodiments, the present invention relates to a method for administering a composition, which comprises:

[0098] (a) a compound of Formula (I): a pharmaceutically acceptable salt or solvate form thereof; and (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof.

[0099] In some embodiments, the present invention relates to a method and / or use for treating psoriatic arthritis by administering a composition, which comprises:

[0100] (a) a compound of Formula (I):

[0101] a pharmaceutically acceptable salt or solvate form thereof; and

[0102] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof. In some embodiments, the present invention relates to the method and / or use, which comprises administering multiple doses of the composition of the present invention.

[0103] In some embodiments, the present invention relates to a method and / or use for treating psoriatic arthritis by administering a composition, which comprises:

[0104] (a) a compound of Formula (I):

[0105] a pharmaceutically acceptable salt or solvate form thereof; and

[0106] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof; where the composition is administered to the subject for at least 16 weeks.

[0107] In some embodiments, the present invention relates to a method and / or use, which comprises the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof which is a hydrochloride salt of the compound of Formula (I) or solvate thereof.

[0108] In some embodiments, the present invention relates to a method and / or use for the treatment of psoriatic arthritis. In some embodiments, the psoriatic arthritis is moderate to severe.

[0109] The compositions of the present invention can be administered to a subject or patient by any means in accordance with therapeutic administration, which accomplishes the intended purpose or pharmaceutical efficacy. Examples include administration by oral, parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal, topical, buccal or ocular routes. In some embodiments, the administration of the composition of the present invention is adapted for oral administration.

[0110] In some embodiments of the present invention, the method and / or use comprises orally administering the composition.

[0111] In some embodiments of the present invention, the method and / or use comprises administering the composition daily.

[0112] In some embodiments of the method and / or use of the invention, the composition is a tablet or the composition is formulated in a tablet comprised of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof and at least one or more pharmaceutically acceptable excipients. In some embodiments of the method and / or use of the invention, the composition is a tablet.

[0113] In some embodiments, the IL-23 receptor antagonist (e.g., the compound of formula (I) or pharmaceutically acceptable salt or solvate) has systemic activity. In some embodiments, the IL-23 receptor antagonist (the compound of formula (I) or pharmaceutically acceptable salt or solvate) is orally administered once daily. In some embodiments, the IL-23 receptor antagonist (the compound of formula (I) or pharmaceutically acceptable salt or solvate) is orally administered twice daily.

[0114] In some embodiments, the present invention relates to the method and / or use, which comprises orally administering the compound of formula (I) or pharmaceutically acceptable salt or solvate thereof. In some embodiments, the present invention relates to the method and / or use, which comprises orally administering the composition or the compound of formula (I) or pharmaceutically acceptable salt or solvate thereof in a fasted state.

[0115] In some embodiments, the present invention relates to the method and / or use, which comprises orally administering the composition or compound in a fed state.

[0116] In some embodiments, the subject is administered the composition in concurrent or sequential treatment periods. In some embodiments, the subject is administered the composition in concurrent treatment periods. In some embodiments, the subject is administered the composition in sequential treatment periods.

[0117] In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for from about 12 weeks to about 52 weeks, such as from about 12 weeks to about 48 weeks, from about 12 weeks to about 44 weeks, from about 12 weeks to about 40 weeks, from about 12 weeks to about 36 weeks, from about 12 weeks to about 32 weeks, from about 12 weeks to about 28 weeks, from about 12 weeks to about 24 weeks, from about 12 weeks to about 20 weeks, or from about 14 weeks to about 18 weeks. In some embodiments, the present invention relates to a method and / or use. the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 12 weeks, about 13 weeks, about 14 weeks, about 15 weeks, about 16 weeks, about 17 weeks, about 18 weeks, about 19 weeks, or about 20 weeks. In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 14 weeks. In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 15 weeks. In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 16 weeks. In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 17 weeks. In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject for about 18 weeks.

[0118] In some embodiments, the present invention relates to a method and / or use, the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is administered to the subject daily for 16 weeks.

[0119] In some embodiments, the present invention relates to the method and / or use for treating psoriatic arthritis, which includes the composition that has: (a) 200 mg of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof; and (b) one or more pharmaceutically acceptable excipients.

[0120] In some embodiments, the method and / or use as described throughout the specification includes administering a composition, which comprises:

[0121] (a) 200 mg of the compound of Formula (I):

[0122] a pharmaceutically acceptable salt or solvate form thereof; and

[0123] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof. In some embodiments, the present invention relates to the method and / or use for treating psoriatic arthritis, which includes the composition that has: (a) 400 mg of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof; and (b) one or more pharmaceutically acceptable excipients.

[0124] In some embodiments, the method and / or use as described throughout the specification includes administering a composition, which comprises:

[0125] (a) 400 mg of the compound of Formula (I): a pharmaceutically acceptable salt or solvate form thereof; and

[0126] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof.

[0127] In some embodiments, the present invention relates to the method and / or use for treating psoriatic arthritis by administering a composition that comprises: (a) 200 mg of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate form thereof; and (b) one or more pharmaceutically acceptable excipients.

[0128] In some embodiments, the method and / or use as described throughout the specification includes administering a composition, which comprises: (a) 200 mg of a hydrochloride salt of the compound of Formula (I) in a crystalline form:

[0129] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof.

[0130] In some embodiments, the method and / or use as described throughout the specification includes administering a composition, which comprises:

[0131] (a) 400 mg of a hydrochloride salt of the compound of Formula (I) in a crystalline form:

[0132]

[0133] (b) one or more pharmaceutically acceptable excipients; to a subject in need thereof.

[0134] In some embodiment, a method for treating psoriatic arthritis in a subject in need thereof, comprises orally administering a pharmaceutical composition comprising a hydrochloride salt of and one or more excipients selected from the group consisting of colloidal anhydrous silica, silicified microcrystalline cellulose, crospovidone, and magnisum sterate, wherein the amount of the compound of formula (I) in the hydrochloride salt is equivalent to about 200mg, and wherein the pharmaceutical composition is administered once daily. In some embodiments, the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment. In some embodiments, the pharmaceutical composition comprises about 4.0 mg of colloidal anhydrous silica, about 741 mg of silicified microcrystalline cellulose, about 50 mg crospovidone, and about 5 mg magnisum sterate. In some embodiments, the pharmaceutical composition further comprises a coating. In some embodiments, the pharmaceutical composition further comprises about 30 mg coating. In some embodiments, the coating is Opadry QX 321A220063 Yellow coating. In some embodiments, the pharmaceutical composition is in a tablet form.

[0135] In some embodiments, the subject takes the pharmaceutical composition after waking up in the morning before food intake and abstain from food intake for at least 30 minutes after administration of the pharmaceutical composition. In some embodiments, the subject takes the pharmaceutical composition with water only. In some embodiments, the subject takes the pharmaceutical composition with coffee, tea, or water only. In some embodiments, the subject takes the pharmaceutical composition with black coffee or tea. In some embodiments, the pharmaceutical composition is in a form of a tablet and the subject takes the tablet by preparing a suspension by dissolving the tablet in water.

[0136] In some embodiments, the subject is at least 12 years old. In some embodiments, the subject has mild, moderate, or severe hepatic impairment. In some embodiments, the subject should not receive any live vaccine treatment during the administration of the pharmaceutical composition.

[0137] In some embodiments, the subject takes a Tuberculosis (TB) test before receiving the pharmaceutical composition comprising the compound of formula (I). In some embodiments, the subject takes a TB test and is tested negative before being treated with the pharmaceutical composition comprising the compound of formula (I). In some embodiments, the subject tested positive for TB first receives TB treatment before being treated with the pharmaceutical composition comprising the compound of formula (I).

[0138] In some embodiments, the present invention relates to the method and / or use, where before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with a biologic agent for psoriatic arthritis. In some embodiments, the present invention relates to the method and / or use, where the biologic agent for psoriatic arthritis is an anti-IL-23 antibody, an anti-IL-17 or anti-IL-12 / 23 antibody, an anti-TNFa antibody, an agent that modulates B cells, or an agent that modulates T cells.

[0139] In some embodiments, the present invention relates to the method and / or use, where before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with a JAK inhibitor or a PDE4 inhibitor.

[0140] In some embodiments, the present invention relates to the method and / or use, where before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with an immunosuppressant. In some embodiments, the present invention relates to the method and / or use, where the immunosuppressant is methotrexate, azathioprine, cyclosporine. 6-thioguanine, mercaptopurine, mycophenolate mofetil, or tacrolimus.

[0141] Efficacy of the method and / or use of the present invention can be assessed by a number of methods or criteria, as described above and below. In some embodiments, a subject’s response to the method and / or use of the present disclosure can be measured by a PASI response.

[0142] In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 75 response. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 75 response at Week 16 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 75 response at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 75 response at Week 16 of treatment and maintains the PASI 75 response through Week 52 of treatment.

[0143] In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 90 response. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 90 response at Week 16 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 90 response at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 90 response at Week 16 of treatment and maintains the PASI 90 response through Week 52 of treatment.

[0144] In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PASI 100 response. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PAST 100 response at Week 16 of treatment. Tn some embodiments, the present invention relates to the method and / or use, where the subject achieves a PAST 100 response at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves a PAST 100 response at Week 16 of treatment and maintains the PASI 100 response through Week 52 of treatment.

[0145] In some embodiments, the present invention relates to the method and / or use, where the subject achieves a decrease in PASI score from baseline. In some embodiments, the subject achieves at least a 14-point decrease in PASI score. In some embodiments, the subject achieves at least a 15-point decrease in PASI score. In some embodiments, the subject achieves at least a 16-point decrease in PASI score. In some embodiments, the subject achieves at least a 17-point decrease in PASI score. In some embodiments, the subject achieves at least an 18-point decrease in PASI score. In some embodiments, the present invention relates to the method and / or use, where the subject achieves the decrease in PASI score at Week 16 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves the decrease in PASI score at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves the decrease in PASI score at Week 16 of treatment and maintains the decrease in PASI score through Week 52 of treatment.

[0146] In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 or 1. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 or 1 at Week 16 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 or 1 at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 or 1 at Week 16 of treatment and maintains the IGA score of 0 or 1 through Week 52 of treatment.

[0147] In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 at Week 16 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 at Week 52 of treatment. In some embodiments, the present invention relates to the method and / or use, where the subject achieves an Investigator’s Global Assessment (IGA) score of 0 at Week 16 of treatment and maintains the IGA score of 0 through Week 52 of treatment.

[0148] In some embodiments, the present invention relates to the method and / or use, which includes determining frequency and type of related adverse events. In some embodiments, the present invention relates to the method and / or use, which includes determining frequency and type of adverse events leading to discontinuation of administering the composition of the present invention.

[0149] In some embodiments, the present invention relates to the method and / or use, which includes determining laboratory parameters and change in laboratory parameters in a subject over time. In some embodiments, the present invention relates to the method and / or use, which includes determining systolic and diastolic blood pressure in a subject over time.

[0150] In some embodiments, the present invention relates to the method and / or use, which includes determining change in levels of skin and blood biomarkers in a subject over time.

[0151] In some embodiments, the present invention relates to the method and / or use, which includes assessing treatment satisfaction domains using the Treatment Satisfaction Questionnaire for Medications-9 items (TSQM-9). In some embodiments, the present invention relates to the method and / or use, which includes assessing treatment satisfaction domains using the Treatment Satisfaction Questionnaire for Medications-9 items (TSQM-9) at Week 16 of treatment.

[0152] (a) about 200 mg of a hydrochloride salt of a compound of Formula (I): a solvate thereof; and

[0153] (b) one or more pharmaceutically acceptable excipients; to an adult human subject in need thereof; where the adult human subject is a candidate for phototherapy or systemic therapy; and the hydrochloride salt of a compound of Formula (I) or solvate thereof is administered to the adult human subject daily for at least 16 weeks.

[0154] In some embodiments, a method and / or use for treating moderate to severe plaque psoriatic arthritis comprises orally administering daily a composition that includes:

[0155] (a) about 400 mg of a hydrochloride salt of a compound of Formula (I):

[0156] (b) one or more pharmaceutically acceptable excipients; to an adult human subject in need thereof; where the adult human subject is a candidate for phototherapy or systemic therapy; and the hydrochloride salt of a compound of Formula (I) or solvate thereof is administered to the adult human subject daily for at least 52 weeks.

[0157] In some embodiments, a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a hydrochloride salt of the compound of Formula (I):

[0158] to a patient in need thereof.

[0159] 4. The method of claim 42, comprising administering a hydrochloride salt of the compound of formula (I) once daily, and wherein the amount of the compound of formula (I) in the hydrochloride salt is equivalent to about 200 mg.

[0160] 5. The method of clam 42 or 43, wherein the hydrochloride salt of the compound of Formula (I) is in a crystalline form.

[0161] 6. The method of any one of claims 42 to 44, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

[0162] In other aspects, the present invention relates to an assay method for evaluating a dose response of a compound of Formula (I) versus placebo in treatment of moderate to severe plaque psoriatic arthritis, where the compound of Formula (I) or pharmaceutically acceptable salt is a hydrochloride salt of a compound of Formula (I).

[0163] Some embodiments relate to a method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a pharmaceutical composition comprising a hydrochloride salt of a compound of Formula (I):

[0164] and one or more excipients selected from the group consisting of colloidal anhydrous silica, silicified microcrystalline cellulose, crospovidone. and magnisum sterate, wherein the amount of the compound of formula (I) in the hydrochloride salt is equivalent to about 200mg, and wherein the pharmaceutical composition is administered once daily.

[0165] In some embodiments, the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

[0166] In some embodiments, the pharmaceutical composition comprises about 4.0 mg of colloidal anhydrous silica, about 741 mg of silicified microcrystalline cellulose, about 50 mg crospovidone, and about 5 mg magnisum sterate. In some embodiments, the pharmaceutical composition further comprises a coating. In some embodiments, tthe pharmaceutical composition further comprises about 30 mg coating. In some embodiments, the coating is Opadry QX 321A220063 Yellow coating. In some embodiments, the pharmaceutical composition is in a tablet form. In some embodiments, the subject takes the pharmaceutical composition after waking up in the morning before food intake and abstain from food intake for at least 30 minutes after administration of the pharmaceutical composition. In some embodiments, the subject takes the pharmaceutical composition with water only. In some embodiments, the subject is at least 12 years old. In some embodiments, the subject has mild, moderate, or severe hepatic impairment. In some embodiments, the subject should not receive any live vaccine treatment during the administration of the pharmaceutical composition.

[0167] EXAMPLES

[0168] Example 1. Study Evaluating the Efficacy and Safety of IL-23 receptor antagonist peptide for the Treatment of Biologic-naive Participants with Active Psoriatic Arthritis

[0169] IL-23 receptor antagonist peptide as used in this example refers to a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, specifically a hydrochloride salt of compound of Formula (I) in a crystalline form.

[0170] Described below is a multicenter, randomized, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of the hydrochloride salt of the compound of Formula (I) for the treatment of psoriatic arthritis who have not previously been treated with any biologic agents for PsA or PsO (biologic-naive population). This study is a 52-week Phase 3 study with a 52-week blinded LTE (N=540).

[0171] STUDY ARMS AND DURATION

[0172] • At Week 0, approximately 540 participants are randomized in a 5:5:5 :3 ratio to receive treatment in 1 of the following 4 treatment arms:

[0173] • Group I (N=150): 200 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 200 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0174] • Group II (N=150): 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0175] • Group III (N=150): Placebo once daily. Starting at Week 16 participants randomized to this group will cross over to receive 200 mg or 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 200 mg or 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0176] • Group IV (N=90): Ustekinumab 45 mg or 90 mg (as per local label) administered subcutaneously at Weeks 0, 4, 16, 28, and 40. Starting at Week 52, participants randomized to this group who enroll in the LTE will cross over to receive 200 mg or 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0177] • At Week 16. participants in the placebo group (Group III) who are still on study treatment will be re -randomized to cross over in a 1:1 ratio to receive IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg or 400 mg once daily starting from Week 16 and through Week 100. Participants in the other 3 groups (Groups I, II. and IV) will continue to receive the treatment they have received prior to Week 16. Participants in Group I, II, and III will receive ustekinumab placebo SC injections at Week 0, 4, 16, 28 and 40 to maintain the blind.

[0178] • At Week 52, participants in the ustekinumab group (Group IV) who are still on treatment will be re-randomized to cross in a 1:1 ratio to receive IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg or 400 mg once daily starting from Week 52 through Week 100. Participants in Groups I and II will continue to receive the treatment they have received prior to Week 52. Participants in Group III will continue to receive the treatment they have received starting from Week 16 and prior to Week 52.

[0179] • Randomization at Week 0 and re-randomization at Week 16 and Week 52 will be performed using permutated block randomization stratified by the following 2 randomization stratification factors to assure relatively even treatment balance within each stratum defined by randomization stratification factors.

[0180] The main study will include the following:

[0181] 5 -week screening period

[0182] 16-week blinded active- reference and placebo-controlled period

[0183] 36-week blinded active-reference period

[0184] Safety follow-up visit 4 weeks after the last dose of the study intervention (for participants not entering the optional LTE and those who prematurely discontinue study intervention)

[0185] • All participants that complete the main study will have the option to participate in the 52-week blinded LTE period (48 weeks of active treatment plus 4 weeks of safety follow-up).

[0186] Description of Interventions

[0187]

[0188]

[0189] Description of Study Arms

[0190] EFFICACY EVALUATIONS

[0191] Psoriatic Arthritis Response Evaluations

[0192] Joint count (tender and swollen)

[0193] American College of Rheumatology Response

[0194] Dactylitis Assessment

[0195] Enthesitis Assessments (LEI and SPARCC)

[0196] Physician Global Assessment of Disease Activity

[0197] Disability Index of the Health Assessment Questionnaire

[0198] Minimal Disease Activity

[0199] Very Low Disease Activity

[0200] Disease Activity Score 28

[0201] Disease Activity Index for Psoriatic Arthritis

[0202] Psoriatic Arthritis Responder Criteria

[0203] Psoriatic Arthritis Disease Activity Score

[0204] Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein Response (ASDAS- CRP)

[0205] Psoriasis Response Evaluations

[0206] Psoriasis Area and Severity Index

[0207] Investigator’s Global Assessment

[0208] Body Surface Area

[0209] Modified Nail Psoriasis Severity Index

[0210] Physician’s Global Assessment of Fingernail Psoriasis Patient-reported Outcomes

[0211] Functional Assessment of Chronic Illness Therapy - Fatigue

[0212] PsA Impact of Disease

[0213] 36-item Short Form Survey

[0214] Participant Assessment of Psoriatic Arthritis Pain

[0215] Participant Assessment of Psoriasis and Arthritis Activity

[0216] Participant Assessment of Psoriatic Disease Activity

[0217] Bath Ankylosing Spondylitis Disease Activity

[0218] EQ-5D-5L

[0219] Work Productivity and Activity Impairment Questionnaire

[0220] PHARMACOKINETIC EVALUATIONS

[0221] Plasma samples will be used to evaluate the pharmacokinetics of IL-23 RECEPTOR ANTAGONIST PEPTIDE.

[0222] MMUNOGENICITY EVALUATIONS

[0223] Serum samples will be evaluated for antibodies to IL-23 RECEPTOR ANTAGONIST PEPTIDE.

[0224] PHARMACODYNAMIC AND BIOMARKER EVALUATIONS

[0225] Biomarker samples will be collected to examine the biologic response to treatment and to identify biomarkers that are relevant to IL-23 RECEPTOR ANTAGONIST PEPTIDE efficacy and / or PsA disease progression, where local regulations permit. Assessments may include the evaluation of relevant biomarkers in serum and whole blood RNA as specified in the SoA.

[0226] Blood samples for PD analysis of serum IL-23 pathway cytokines and PsA-associated biomarkers may be collected at predetermined time points as outlined in the SoA. PHARMACOGENOMIC (DNA) EVALUATIONS

[0227] A pharmacogenomic blood sample may be collected to allow for pharmacogenomic research, where local regulations permit. Participation in pharmacogenomic research is optional. SAFETY EVALUATIONS

[0228] Safety assessments for all participants will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs). clinical laboratory assessments (hematology, chemistry including lipid panel, pregnancy testing, and urinalysis), vital signs measurements including blood pressure, electrocardiograms, suicidal ideation and behavioral risk monitoring (Columbia-Suicide Severity Rating Scale), and tuberculosis (TB) evaluations.

[0229] STATISTICAL METHODS

[0230] In general, descriptive statistics, such as mean, SD, median, IQ range, minimum, and maximum for continuous variables, and counts and percentages for discrete variables will be used to summarize most data.

[0231] Treatment comparisons between each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 mg or 400 mg) and the placebo group will be performed through Week 16; after Week 16, treatment comparisons will not be performed. No statistical comparison will be performed between the ustekinumab group and any IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group or between the ustekinumab group and the placebo group, and only summary statistics will be provided.

[0232] Treatment comparisons will be performed with 2-sided tests. The Type I error will be controlled over the multiplicity-controlled primary and secondary endpoints at a significance level of <0.05. The list of the multiplicity-controlled primary and secondary endpoints, and tThe approach to control the Type I error for multiplicity across the primary and controlled secondary endpoints will be specified in the SAP. For each multiplicity-controlled endpoint, both adjusted and nominal p-values for treatment comparisons will be provided. For endpoints that are not multiplicity-controlled, nominal p-values will be presented.

[0233] For the primary endpoint (ACR20 at Week 16) and other binary efficacy endpoints through Week 16, treatment comparisons will generally be performed using a Cochran-ManteL Haenszel (CMH) test stratified by randomization stratification factors. The magnitude of the treatment difference will be estimated by the difference in response rates between the IL-23 RECEPTOR ANTAGONIST PEPTIDE and placebo groups with a 95% confidence interval (CI) calculated based on Wald statistics. In these analyses, participants with missing data will be imputed as not achieving the said binary endpoint. The Mantel Fleiss criterion will be used to determine the appropriateness of using the CMH test for each treatment comparison. If the Mantel Fleiss criterion is not satisfied, the Fisher’s exact test will be used for treatment comparisons.

[0234] For secondary continuous efficacy endpoints (change from baseline in HAQ-DI score at

[0235] Week 16, change from baseline in enthesitis score at Week 16 in participants with enthesitis at baseline, change from baseline in dactylitis score at Week 16 in participants with dactylitis at baseline, change from baseline in SF-36 PCS at Week 16, and change from baseline in FACIT- Fatigue at Week 16), treatment comparisons will be performed using an analysis of covariance (ANCOVA) model based on data with missing imputed by the multiple imputation (MI) under the assumption of missing at random (MAR). The explanatory variables of the ANCOVA model will include treatment group, baseline score, and randomization stratification factors. The model will include data from all the 4 treatment groups (IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg, IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg, placebo, ustekinumab) at the visit of interest. The treatment difference between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group versus the placebo group will be tested for each MI dataset and then the analysis results across all MI datasets will be combined. No treatment difference between the ustekinumab group versus any other group will be calculated or tested.

[0236] For all other continuous efficacy endpoints through Week 16, treatment comparisons will be performed, in general, using a Mixed-Effect Model for Repeat Measures (MMRM) under the assumption of MAR. The model will include all available data from all the treatment groups (IL- 23 RECEPTOR ANTAGONIST PEPTIDE 400 mg, IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg, placebo, ustekinumab) through Week 16. The treatment difference between a IL-23 RECEPTOR ANTAGONIST PEPTIDE group and the placebo group will be estimated by the difference in the least square means (LSmeans). The 95% Cis for the differences in LSmeans and p- values will be calculated. No treatment difference between the ustekinumab group versus any other group will be calculated or tested.

[0237] All the endpoints will be tested using the data from this study only.

[0238] The enthesitis and dactylitis related endpoints are only applicable to those participants with the said condition at baseline (ie, a subgroup of the study participants) and therefore will also be tested through Week 16 using the combined data from IL-23 RECEPTOR ANTAGONIST PEPTIDEPSA3001 and IL-23 RECEPTOR ANTAGONIST PEPTIDEPSA3002 for each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 mg or 400 mg) versus the placebo group. The details for 2-study data combination and treatment comparisons based on the combined data will be specified in the SAP.

[0239] Primary Endpoints / Estimand

[0240] In this study, the primary endpoint is ACR20 response at Week 16.

[0241] The primary estimand (ie, a precise definition of the primary targeted treatment effect) is defined by the following 5 attributes (treatment condition of interest versus alternative treatment condition, population, variable (endpoint), intercurrent events and handling strategies, and population-level summary):

[0242] Treatment Condition of Interest Versus Alternative Treatment Condition

[0243] Treatment condition of interest:

[0244] IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg: IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg once daily up to Week 16 IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg: IL-23 RECEPTOR

[0245] ANTAGONIST PEPTIDE 400 mg once daily up to Week 16

[0246] Alternative treatment condition:

[0247] Placebo: Placebo once daily up to Week 16

[0248] Population: Participants with active PsA Variable: A binary response variable (response / non-response) where response is defined as achieving ACR20 response at Week 16 and participants experiencing any ICE in categories 1-3 as outlined below prior to Week 16 are considered as not achieving ACR20 response at Week 16.

[0249] Intercurrent Events (ICE) and Corresponding Strategies:

[0250] Population-level summary: The difference in proportion of participants achieving an ACR20 response at Week 16 between each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group versus the placebo group. Primary Endpoint Analysis

[0251] The primary analysis of the primary endpoint, ACR20 response at Week 16, will be based on the Primary Estimand defined above. After accounting for the ICEs for the Primary Estimand, participants with missing ACR20 response status will be considered as not having achieved an ACR20 response at Week 16 (ie, non-responder imputation). The treatment difference between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group versus the placebo group will be tested using a CMH test stratified by the randomization stratification factors. The magnitude of the treatment difference will be estimated by the difference in ACR20 response rates between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group and placebo groups with a 95% CI calculated based on Wald statistics.

[0252] The study will be considered positive if at least one IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 or 400 mg) is significantly better, at a 2-sided a=0.025. than the placebo group.

[0253] OBIECTIVES AND ENDPOINTS

[0254] All participants that complete the main study will have the option to participate in the 52- week blinded LTE period (48 weeks of active treatment plus 4 weeks of safety follow-up).

[0255] Efficacy, safety, PK, immunogenicity, and biomarkers will be assessed according to the SoA.

[0256] An independent joint assessor with adequate training and experience in performing joint assessments will be designated at each study site to perform joint assessments, as well as dactylitis and enthesitis assessments.

[0257] In participants who consent (where the local regulations permit), a pharmacogenomic (DNA) blood sample will be collected.

[0258] There are 3 planned database locks (DBLs) at Week 24 (the primary DBL), at Week 52, and at Week 104 (ie. the final DBL at the end of the study). The primary DBL will occur at Week 24 (Week 24 DBL) when all participants in the study have completed their Week 24 visit or have discontinued study participation prematurely prior to Week 24. The Week-52 DBL will occur when all participants have completed their Week 52 visit or have discontinued study participation prematurely prior to Week 52. The Week- 104 (final) DBL will occur when all participants have completed their Week-104 visit or have discontinued study participation prematurely prior to Week 104. Additional DBLs may occur to support publication or regulatory submissions including when additional time may be needed to reach country- specific data requirements.

[0259] The study will remain blinded to the treatment assignment until after the Week- 104 DBL, after which unblinding for the study will occur. At Week-24 and Week-52 DBLs, selected Sponsor staff will be unblinded for the purpose of data analysis and data review. The list of selected Sponsor staff who are unblinded and at which unblinding level (treatment group level or participant level) will be specified in the Unblinding Plan for Week-24 DBL and for Week-52 DBL.

[0260] An Independent Data Monitoring Committee will be commissioned for this study. Refer to Committees Structure in Appendix 2: Regulatory, Ethical, and Study Oversight Considerations for details.

[0261] A diagram of the study design is provided in Section 1.2, Schema. Scientific Rationale for Study Design

[0262] Blinding, Control, Study Phase / Periods, Intervention Groups

[0263] Consistent with health authority guidelines, placebo control will be used to establish the frequency and magnitude of changes in clinical endpoints that may occur in the absence of active intervention. Additionally, all participants are permitted to use selected background medications for PsA, as described in Section 6.9. Randomization will be used to minimize bias in the assignment of participants to intervention groups, to increase the likelihood that known and unknown participants attributes (eg, demographic and baseline characteristics) are evenly balanced across intervention groups, and to enhance the validity of statistical comparisons across intervention groups. Blinded intervention will be used to reduce potential bias during data collection and evaluation of clinical endpoints.

[0264] DNA and Biomarker Collection

[0265] It is recognized that genetic variation can be an important contributory factor to interindividual differences in intervention distribution and response and can also serve as a marker for disease susceptibility and prognosis. Pharmacogenomic research may help to explain interindividual variability in clinical outcomes and may help to identify population subgroups that respond differently to an intervention. The goal of the pharmacogenomic component is to collect DNA to allow the identification of genetic factors that may influence the PK, PD, efficacy, safety or tolerability of IL-23 RECEPTOR ANTAGONIST PEPTIDE and to identify genetic factors associated with PsA.

[0266] Biomarker samples will be collected where local regulations permit to evaluate the mechanism of action of IL-23 RECEPTOR ANTAGONIST PEPTIDE that may help to explain interindividual variability in clinical outcomes or identify population subgroups that respond differently to an intervention. The goal of the biomarker analyses is to evaluate the PD of IL-23 RECEPTOR ANTAGONIST PEPTIDE and aid in evaluating the intervention-clinical response relationship.

[0267] Biomarker and optional pharmacogenomic samples may be used to help address emerging issues and to enable the development of safer, more effective, and ultimately individualized therapies. Sample collection and testing will comply with local regulations. A pharmacogenomic blood sample may be collected to allow for pharmacogenomic research, where local regulations permit. Participation in the pharmacogenomic research is optional.

[0268] Health Economics Data Collection

[0269] The EQ-5D-5L will be used in this study to derive health states that can be used in health economic evaluations. The WPAI-PsA will be used to measure the effect of PsA on work productivity and regular activities.

[0270] Participant Input Into Design

[0271] Patient input on protocol design was obtained and found acceptable. Patient input was used to design the following elements of this study:

[0272] • Since participants have different sleep patterns, the once-daily dose regimen will be taken ‘upon waking’ with no food at least 2 hours before and 30 mins after instead of upon waking in the morning.

[0273] • Taking the once-daily oral dose regimen and 5 subcutaneous injections over a 52- week period was acceptable and considered manageable for participants with active PsA.

[0274] • Eligibility criteria were considered inclusive and favorable for recruiting participants with active PsA.

[0275] The results of the study may be made available to all participants through plain language summary, a technical summary results of clinicaltrials.gov, and / or clinicaltrialsregister.eu and / or other national registries at the conclusion of the study according to local standards / restrictions.

[0276] Study-specific Ethical Design Considerations

[0277] Potential participants will be fully informed of the risks and requirements of the study, and during the study, participants will be given any new information that may affect their decision to continue participation. They will be told that their consent to participate in the study is voluntary and may be withdrawn at any time with no reason given and without penalty or loss of benefits to which they would otherwise be entitled. Only participants who are fully able to understand the risks, benefits, and potential AEs of the study, and provide their consent voluntarily will be enrolled. Written consent may be obtained through various sources (eg, paper or electronic such as eConsent, eSignature, or digital signature) as determined by regulations as well as study and / or patient preferences.

[0278] The primary ethical concern for participants is for participants in the placebo control arm who will not receive active treatment. This concern will be mitigated by the cross-over design that allows participants in the placebo group to receive active treatment with IL-23 RECEPTOR ANTAGONIST PEPTIDE starting at Week 16.

[0279] Participants will be discontinued from study intervention if the investigator considers it is in the best interest of the participant (Section 7.1).

[0280] The total blood volume to be collected is considered to be an acceptable amount of blood to be collected over this time period from the population in this study based upon the standard of the American Red Cross. For more details regarding blood collection, see Blood Sample Collection in Section 8. STUDY POPULATION

[0281] Screening for eligible participants will be performed within 5 weeks prior to administration of the study intervention. Refer to Section 5.4, Screen Failures, for conditions under which the repeat of any screening procedures are allowed.

[0282] The inclusion and exclusion criteria for enrolling participants in this study are described below. Efforts will be made to ensure broad representation in terms of race, ethnicity, and sex. If there is a question about these criteria, the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a participant in the study. Waivers are not allowed.

[0283] For a discussion of the statistical considerations of participant selection, refer to Section 9.5, Sample Size Determination.

[0284] Inclusion Criteria: Each potential participant must satisfy all of the following criteria to be enrolled in the study

[0285] Type of Participant and Disease Characteristic(s)

[0286] Have a diagnosis of PsA for at least 3 months before the first administration of study intervention and meet classification criteria for Psoriatic Arthritis (CASPAR) at screening.

[0287] Have active PsA as defined by At least 3 swollen joints and at least 3 tender joints at screening and at baseline and C-reactive protein (CRP) >0.1 mg / dL at screening from the central laboratory.

[0288] A one-time repeat assessment of CRP level is allowed during the screening phase and the Investigator may consider the participant eligible if the test result is within acceptable range on repeat testing in the central laboratory.

[0289] Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis.

[0290] Have active plaque psoriasis with at least one psoriatic plaque of >2 cm diameter or nail changes consistent with psoriasis.

[0291] Participants must be considered in the opinion of the investigator, to be a suitable candidate for treatment with ustekinumab per locally-approved labeling and have no contraindications to receive ustekinumab per local label.

[0292] Have active PsA despite current or previous non-biologic DMARD and / or apremilast.

[0293] Non-biologic DMARD (limited to MTX, SSZ, HCQ, or LEF) therapy is defined as taking a non-biologic DMARD for at least 12 weeks before first administration of study intervention, or evidence of non-biologic DMARD intolerance.

[0294] Apremilast therapy is defined as taking apremilast at the marketed dose approved in the country where the study is being conducted for at least 12 weeks before first administration of study intervention, or evidence of apremilast intolerance.

[0295] If currently using non-biologic DMARDs (limited to MTX, SSZ, HCQ, or LEF), participants should have started treatment at least 12 weeks prior and the dose must be stable for at least 4 weeks before first administration of study intervention and should have no serious toxic side effects attributable to the non-biologic DMARD. If currently not using MTX, SSZ, or HCQ, must not have received for at least 4 weeks before first administration of study intervention. If currently not using LEF, must not have received for at least 12 weeks before first administration of study intervention. a)If using MTX, the route of administration and dose must be stable and the dose must be < 25 mg / week. b) If receiving SSZ, the dose must be stable and <3 g / day c)If receiving HCQ, the dose must be stable and <400 mg / day d) If receiving LEF, the dose must be stable and <20 mg / day (NOTE: use of LEF and MTX combination therapy is not allowed)

[0296] If using apremilast at baseline, participants must be on a stable dose and <30 mg twice daily for at least 12 weeks before first administration of study intervention. If currently not using apremilast, the participant must not have received apremilast within 4 weeks before first administration of study intervention.

[0297] If using NSAIDs for PsA at baseline, participants must be on a stable dose for at least 2 weeks before first administration of study intervention. The maximum allowed dose is the marketed dose approved in the country where the study is being conducted. If currently not using NSAIDs for PsA, must not have received NSAIDs for PsA within 2 weeks before first administration of study intervention.

[0298] If using oral corticosteroids at baseline, participants must be on a stable dose equivalent to <10 mg of prednisone / day for at least 2 weeks before first administration of study intervention. If currently not using oral corticosteroids, the participant must not have received oral corticosteroids within 2 weeks before first administration of study intervention.

[0299] Sex and Contraceptive / Barrier Requirements

[0300] A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (P-hCG) at screening and a negative urine pregnancy test at Week 0 prior to administration of study intervention.

[0301] Criterion modified per Amendment 1

[0302] 10.1. A female participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 15 weeks after the last administration of SC study intervention and 4 weeks after the last dose of oral study intervention administration.

[0303] Criterion modified per Amendment 1

[0304] 11.1. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 15 weeks after the last administration of SC study intervention and 4 weeks after the last dose of oral study intervention administration.

[0305] Criterion modified per Amendment 1

[0306] 12.1. A female participant must be (as defined in Appendix 4: Contraceptive Guidance) a. Not of childbearing potential OR b.Of childbearing potential and

[0307] Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 15 weeks after the last administration of SC study intervention and 4 weeks after last dose of oral study intervention administration - the end of relevant systemic exposure. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. Examples of highly effective methods of contraception are located in Appendix 4: Contraceptive Guidance.

[0308] Note: If a participant’s childbearing potential changes after start of the study (eg. a premenarchal female participant experiences menarche) or the risk of pregnancy changes (eg, a female participant who is not hetero sexually active becomes active), a female participant must begin using a highly effective method of contraception.

[0309] Note: the period of 4 weeks (in criteria #10, 11, and 12 above) applies to IL-23 RECEPTOR ANTAGONIST PEPTIDE and the period of 15 weeks applies to ustekinumab. For participants receiving MTX, the period (after the last administration of each drug) is 6 months or as per local approved labeling. For participants receiving LEF, the period is 2 years or as per local approved labeling unless the participant has completed an accelerated drug elimination treatment.

[0310] Criterion modified per Amendment 1

[0311] 19.1. Agree not to receive a live virus vaccine during the study or within 15 weeks after the last administration of SC study intervention and 4 weeks after the last administration of oral study intervention administration. For live bacterial vaccination, including bacillus Calmette-Guerin (BCG) vaccination, agree not to receive during the study and for 12 months after the last administration of SC study intervention and 4 weeks after last administration of oral study intervention.

[0312] Exclusion Criteria

[0313] Any potential participant who meets any of the following criteria will be excluded from participating in the study:

[0314] Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study. Section 5.4. Screen Failures describes options for retesting. The required source documentation to support meeting the enrollment criteria are noted in Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.

[0315] Lifestyle Considerations

[0316] Participants must be willing and able to adhere to the following lifestyle restrictions to be eligible for participation:

[0317] Prohibited and Restricted Therapies During the Study

[0318] Refer to Section 6.9 for details regarding prohibited and restricted therapy during the study. Refer to Sections 5.1 and 5.2 for allowed, restricted and prohibited concomitant medications and washout periods for prior medications.

[0319] It is recommended to be up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. It is strongly recommended that participants will have completed a locally-approved (or emergency use-authorized) COVID- 19 vaccination regimen at least 2 weeks prior to study-related visits or procedures. Study participants should follow applicable local vaccine labeling, guidelines, and standards-of- care for participants receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrollment (Section 6.9).

[0320] Meals and Dietary Restrictions

[0321] The study intervention must be swallowed whole. Participants will be instructed to take the study intervention at approximately the same time every day upon waking with 240 mL (8 oz) water on an empty stomach (no food intake for at least 2 hours before and for at least 30 minutes after taking the study intervention).

[0322] Activity

[0323] Participants are encouraged to use sun protective measures (such as a hat, sunglasses, protective clothing, sunscreen) during study participation, as ultraviolet exposure may affect psoriasis efficacy assessments.

[0324] Agree to limit prolonged, direct sunlight exposure such as tanning in direct sunlight without sunscreen and avoid artificial sunlight (tanning beds or phototherapy).

[0325] Agree to abstain from excessive exercise (eg, body building, long distance running and cycling) 2-3 days prior to any study visit where chemistry laboratory blood samples are drawn.

[0326] Example 2. A Study of the Efficacy and Safety of Compound of formula (I) in Biologic-experienced Participants with Active Psoriatic Arthritis

[0327] IL-23 receptor antagonist peptide as used in this example refers to a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, specifically a hydrochloride salt of compound of Formula (I) in a crystalline form.

[0328] Described below is • This is a randomized, double-blind, placebo controlled study evaluating the efficacy and safety of IL-23 RECEPTOR ANTAGONIST PEPTIDE for the treatment of participants with active PsA who have been previously treated with 1 biologic agent for PsA or PsO (biologic experienced population).

[0329] OBJECTIVES AND ENDPOINTS

[0330] Study

[0331] The studies related to the primary endpoint are that:

[0332] 1. IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg once daily is superior to placebo with respect to reduction of PsA signs and symptoms as measured by ACR20 response at Week 16.

[0333] 2. IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg once daily is superior to placebo with respect to reduction of PsA signs and symptoms as measured by ACR20 response at Week 16.

[0334] The study will be considered positive if at least 1 of the above 2 hypotheses achieves the statistical significance at a 2-sided a=0.025.

[0335] This study is a 52-week Phase 3 study with a 52-week blinded LTE (N=750).

[0336] An Independent Data Monitoring Committee will be commissioned for this study.

[0337] NUMBER OF PARTICIPANTS

[0338] A target total of 750 participants will be enrolled in the study with a total duration for each participant of up to 2 years.

[0339] STUDY ARMS AND DURATION

[0340] At Week 0, approximately 750 participants will be randomized in a 1:1:1 ratio to receive treatment in 1 of the following 3 treatment arms:

[0341] Group I (N=250): 200 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 200 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0342] Group II (N=250): 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0343] Group III (N=250): Placebo once daily. Starting at Week 16 participants randomized to this group will cross over to receive 200 mg or 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily. Starting at Week 52, participants randomized to this group who enroll in the LTE will continue to receive 200 mg or 400 mg IL-23 RECEPTOR ANTAGONIST PEPTIDE once daily through Week 100, with safety follow-up at Week 104.

[0344] At Week 16. participants in the placebo group (Group III) who are still on-study treatment will be re -randomized to cross over in a 1:1 ratio to receive IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg or 400 mg once daily starting from Week 16 through Week 100. Participants in the other 2 groups (Groups I and II) will continue to receive the treatment they have received prior to Week 16.

[0345] Randomization at Week 0 and re-randomization at Week 16 will be performed using permutated block randomization stratified by the following 3 randomization stratification factors to assure relatively even treatment balance within each stratum defined by randomization stratification factors.

[0346] The 3 randomization stratification factors are based on the following questions:

[0347] 1. What type of prior biologic therapy has the participant used (anti-TNFa versus anti-IL- 17 versus other biologic)?

[0348] 2. Does the participant use non-biologic DMARD (MTX, SSZ, HCQ, LEF) and / or apremilast at baseline? (yes / no)

[0349] 3.1s dactylitis present at baseline? (yes / no)

[0350] The main study will include the following:

[0351] 5 -week screening period

[0352] 16-week blinded placebo-controlled period

[0353] 36-week blinded active-treatment period

[0354] Safety follow-up visit 4 weeks after the last dose of the study intervention (for participants not entering the optional LTE and those who prematurely discontinue study intervention)

[0355] All participants that complete the main study will have the option to participate in the 52- week blinded LTE period (48 weeks of active treatment plus 4 weeks of safety follow-up).

[0356]

[0357] Description of Study Arms

[0358] EFFICACY EVALUATIONS

[0359] Psoriatic Arthritis Response Evaluations

[0360] Joint count (tender and swollen)

[0361] American College of Rheumatology Response

[0362] Dactylitis Assessment

[0363] Enthesitis Assessments (LEI and SPARCC)

[0364] Physician Global Assessment of Disease Activity

[0365] Disability Index of the Health Assessment Questionnaire

[0366] Minimal Disease Activity

[0367] Very Low Disease Activity

[0368] Disease Activity Score 28

[0369] Disease Activity Index for Psoriatic Arthritis

[0370] Psoriatic Arthritis Responder Criteria

[0371] Psoriatic Arthritis Disease Activity Score

[0372] Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein Response (ASDAS- CRP)

[0373] Psoriasis Response Evaluations

[0374] Psoriasis Area and Severity Index

[0375] Investigator’s Global Assessment

[0376] Body Surface Area

[0377] Modified Nail Psoriasis Severity Index

[0378] Physician’s Global Assessment of Fingernail Psoriasis

[0379] Patient-reported Outcomes

[0380] Functional Assessment of Chronic Illness Therapy - Fatigue

[0381] PsA Impact of Disease

[0382] 36-item Short Form Survey

[0383] Participant Assessment of Psoriatic Arthritis Pain

[0384] Participant Assessment of Psoriasis and Arthritis Activity

[0385] Participant Assessment of Psoriatic Disease Activity

[0386] Bath Ankylosing Spondylitis Disease Activity

[0387] EQ-5D-5L

[0388] Work Productivity and Activity Impairment Questionnaire

[0389] PHARMACOKINETIC EVALUATIONS

[0390] Plasma samples will be used to evaluate the pharmacokinetics of IL-23 RECEPTOR ANTAGONIST PEPTIDE.

[0391] IMMUNOGENICITY EVALUATIONS

[0392] Serum samples will be evaluated for antibodies to IL-23 RECEPTOR ANTAGONIST PEPTIDE.

[0393] PHARMACODYNAMIC AND BIOMARKER EVALUATIONS

[0394] Biomarker samples will be collected to examine the biologic response to treatment and to identify biomarkers that are relevant to IL-23 RECEPTOR ANTAGONIST PEPTIDE efficacy and / or PsA disease progression, where local regulations permit. Assessments may include the evaluation of relevant biomarkers in serum and whole blood RNA as specified in the SoA.

[0395] Blood samples for PD analysis of serum IL-23 pathway cytokines and PsA-associated biomarkers may be collected at predetermined time points as outlined in the SoA.

[0396] PHARMACOGENOMIC (DNA) EVALUATIONS

[0397] A pharmacogenomic blood sample may be collected to allow for pharmacogenomic research, where local regulations permit. Participation in pharmacogenomic research is optional.

[0398] SAFETY EVALUATIONS

[0399] Safety assessments for all participants will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinical laboratory assessments

[0400] (hematology, chemistry including lipid panel, pregnancy testing, and urinalysis), vital signs measurements including blood pressure, electrocardiograms, suicidal ideation and behavioral risk monitoring (Columbia-Suicide Severity Rating Scale), and tuberculosis (TB) evaluations.

[0401] STATISTICAL METHODS

[0402] In general, descriptive statistics, such as mean, SD, median, IQ range, minimum, and maximum for continuous variables, and counts and percentages for discrete variables will be used to summarize most data.

[0403] Treatment comparisons between each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 mg or 400 mg) and the placebo group will be performed through Week 16; after Week 16, treatment comparisons will not be performed.

[0404] Treatment comparisons will be performed with 2-sided tests. The Type I error will be controlled over the multiplicity-controlled primary and secondary endpoints at a significance level of <0.05. The list of the multiplicity-controlled primary and secondary endpoints, and tThe approach to control the Type I error for multiplicity across the primary and controlled secondary endpoints will be specified in the SAP. For each multiplicity-controlled endpoint, both adjusted and nominal p-values for treatment comparisons will be provided. For endpoints that are not multiplicity-controlled, nominal p-values will be presented.

[0405] For the primary endpoint (ACR20 at Week 16) and other binary efficacy endpoints through Week 16, treatment comparisons will generally be performed using a Cochran-ManteL Haenszel (CMH) test stratified by randomization stratification factors. The magnitude of the treatment difference will be estimated by the difference in response rates between the IL-23 RECEPTOR ANTAGONIST PEPTIDE and placebo groups with a 95% confidence interval (CI) calculated based on Wald statistics. In these analyses, participants with missing data will be imputed as not achieving the said binary endpoint. The Mantel Fleiss criterion will be used to determine the appropriateness of using the CMH test for each treatment comparison. If the Mantel Fleiss criterion is not satisfied, the Fisher’s exact test will be used for treatment comparisons.

[0406] For secondary continuous efficacy endpoints (change from baseline in HAQ-DI score at Week 16, change from baseline in enthesitis score at Week 16 in participants with enthesitis at baseline, change from baseline in dactylitis score at Week 16 in participants with dactylitis at baseline, change from baseline in SF-36 PCS at Week 16, and change from baseline in FACIT-

[0407] Fatigue at Week 16), treatment comparisons will be performed using an analysis of covariance (ANCOVA) model based on data with missing imputed by the multiple imputation (MI) under the assumption of missing at random (MAR). The explanatory variables of the ANCOVA model will include treatment group, baseline score, and randomization stratification factors. The model will include data from all treatment groups (IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg, IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg, placebo) groups at the visit of interest. The treatment difference between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group versus the placebo group will be tested for each MI dataset and then the analysis results across all MI datasets will be combined.

[0408] For all other continuous efficacy endpoints through Week 16, treatment comparisons will be performed, in general, using a Mixed-Effect Model for Repeat Measures (MMRM) under the assumption of MAR. The model will include all available data from all the treatment (IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg, IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg, placebo) groups through Week 16. The treatment difference between a IL-23 RECEPTOR ANTAGONIST PEPTIDE group and the placebo group will be estimated by the difference in the least square means (LSmeans). The 95% Cis for the differences in LSmeans and p-values will be calculated.

[0409] All the endpoints will be tested using the data from this study only.

[0410] The enthesitis and dactylitis related endpoints are only applicable to those participants with the said condition at baseline (ie, a subgroup of the study participants) and therefore will also be tested through Week 16 using the combined data from IL-23 RECEPTOR ANTAGONIST PEPTIDEPSA3001 and IL-23 RECEPTOR ANTAGONIST PEPTIDEPSA3002 for each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 mg or 400 mg) versus the placebo group. The details for 2-study data combination and treatment comparisons based on the combined data will be specified in the SAP.

[0411] Primary Endpoints / Estimand

[0412] In this study, the primary endpoint is ACR20 response at Week 16.

[0413] The primary estimand (ie, a precise definition of the primary targeted treatment effect) is defined by the following 5 attributes (treatment condition of interest versus alternative treatment condition, population, variable (endpoint), intercurrent events and handling strategies, and population-level summary):

[0414] Treatment Condition of Interest Versus Alternative Treatment Condition

[0415] Treatment condition of interest:

[0416] Compound of formula (I) hydrochloride salt- IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg: IL-23 RECEPTOR ANTAGONIST PEPTIDE 200 mg once daily up to Week 16

[0417] Compound of formula (I) hydrochloride salt-IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg: IL-23 RECEPTOR ANTAGONIST PEPTIDE 400 mg once daily up to Week 16

[0418] Alternative treatment condition: Placebo: Placebo once daily up to Week 16

[0419] Population: Participants with active PsA

[0420] Variable: A binary response variable (response / non-response) where response is defined as achieving ACR20 response at Week 16 and participants experiencing any ICE in categories 1- 3 as outlined below prior to Week 16 are considered as not achieving ACR20 response at Week 16.

[0421] Intercurrent Events (ICE) and Corresponding Strategies:

[0422] Population-level summary: The difference in proportion of participants achieving an ACR20 response at Week 16 between each IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group versus the placebo group. Primary Endpoint Analysis

[0423] The primary analysis of the primary endpoint, ACR20 response at Week 16, will be based on the Primary Estimand defined above. After accounting for the ICEs for the Primary

[0424] Estimand, participants with missing ACR20 response status will be considered as not having achieved an ACR20 response at Week 16 (ie, non-responder imputation).

[0425] The treatment difference between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group versus the placebo group will be tested using a CMH test stratified by the randomization stratification factors. The magnitude of the treatment difference will be estimated by the difference in ACR20 response rates between each IL-23 RECEPTOR ANTAGONIST PEPTIDE group and placebo groups with a 95% CI calculated based on Wald statistics.

[0426] The study will be considered positive if at least one IL-23 RECEPTOR ANTAGONIST PEPTIDE dose group (200 mg or 400 mg) is significantly better, at a 2-sided a=0.025, than the placebo group.

[0427] STUDY POPULATION

[0428] Screening for eligible participants will be performed within 5 weeks prior to administration of the study intervention. Refer to Section 5.4, Screen Failures, for conditions under which the repeat of any screening procedures are allowed.

[0429] The inclusion and exclusion criteria for enrolling participants in this study are described below. Efforts will be made to ensure broad representation in terms of race, ethnicity, and sex. If there is a question about these criteria, the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a participant in the study. Waivers are not allowed.

[0430] Sample Size Determination.

[0431] Inclusion Criteria

[0432] Each potential participant must satisfy all of the following criteria to be enrolled in the study:

[0433] Type of Participant and Disease Characteristic(s)

[0434] Have a diagnosis of PsA for at least 3 months before the first administration of study intervention and meet classification criteria for Psoriatic Arthritis (CASPAR) at screening.

[0435] Have active PsA as defined by:

[0436] At least 3 swollen joints and at least 3 tender joints at screening and at baseline

[0437] -AND-

[0438] C-reactive protein (CRP) >0.1 mg / dL at screening from the central laboratory.

[0439] A one-time repeat assessment of CRP level is allowed during the screening phase and the Investigator may consider the participant eligible if the test result is within acceptable range on repeat testing in the central laboratory.

[0440] Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis.

[0441] Have active plaque psoriasis with at least one psoriatic plaque of >2 cm diameter or nail changes consistent with psoriasis.

[0442] Participants must have been previously treated with 1 biologic agent for PsA or psoriasis and the reason for discontinuation must be documented. Reasons for discontinuation may include:

[0443] Lack of benefit to a biologic therapy, as assessed by the treating physician, after at least 12 weeks of abatacept, etanercept, adalimumab, golimumab, or certolizumab pegol therapy (or biosimilar), at least 14 weeks of infliximab (or biosimilar), or 16 weeks of anti-IL-17 therapy at an approved dose for PsA or psoriasis. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or PsA or psoriasis disease activity.

[0444] Intolerance to a biologic therapy for PsA or psoriasis, as assessed by the treating physician.

[0445] Other reason: If no intolerance or lack of benefit, the reason for discontinuation must be documented.

[0446] If currently using non-biologic DMARDs (limited to MTX, SSZ, HCQ, or LEF), participants should have started treatment at least 12 weeks prior and the dose must be stable for at least 4 weeks before first administration of study intervention and should have no serious toxic side effects attributable to the non-biologic DMARD. If currently not using MTX, SSZ, or HCQ, must not have received for at least 4 weeks before first administration of study intervention. If currently not using LEF, must not have received for at least 12 weeks before first administration of study intervention. c.If using MTX, the route of administration and dose must be stable and the dose must be < 25 mg / week.

[0447] If receiving SSZ, the dose must be stable and <3 g / day

[0448] If receiving HCQ, the dose must be stable and <400 mg / day

[0449] If receiving LEF, the dose must be stable and <20 mg / day

[0450] (NOTE: use of LEF and MTX combination therapy is not allowed)

[0451] If using apremilast at baseline, participants must be on a stable dose and <30 mg twice daily for at least 12 weeks before first administration of study intervention. If currently not using apremilast, the participant must not have received apremilast within 4 weeks before first administration of study intervention.

[0452] If using NSAIDs for PsA at baseline, participants must be on a stable dose for at least 2 weeks before first administration of study intervention. The maximum allowed dose is the marketed dose approved in the country where the study is being conducted. If currently not using NSAIDs for PsA, must not have received NSAIDs for PsA within 2 weeks before first administration of study intervention.

[0453] If using oral corticosteroids at baseline, participants must be on a stable dose equivalent to <10 mg of prednisone / day for at least 2 weeks before first administration of study intervention. If currently not using oral corticosteroids, the participant must not have received oral corticosteroids within 2 weeks before first administration of study intervention.

[0454] A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (P-hCG) at screening and a negative urine pregnancy test at Week 0 prior to administration of study intervention.

[0455] A female participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 4 weeks after the last dose of study intervention.

[0456] A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 4 weeks after the last dose of study intervention administration.

[0457] A female participant must be (as defined in Appendix 4: Contraceptive Guidance) d.Not of childbearing potential OR e. Of childbearing potential and

[0458] Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 4 weeks after last dose - the end of relevant systemic exposure. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. Examples of highly effective methods of contraception are located in Appendix 4: Contraceptive Guidance.

[0459] Note: If a participant’s childbearing potential changes after start of the study (eg, a premenarchal female participant experiences menarche) or the risk of pregnancy changes (eg, a female participant who is not hetero sexually active becomes active), a female participant must begin using a highly effective method of contraception.

[0460] The period of 4 weeks (in criteria #9, 10, and 11 above) applies to IL-23 RECEPTOR ANTAGONIST PEPTIDE. For participants receiving MTX, the period (after the last administration of each drug) is 6 months or as per local approved labeling. For participants receiving LEF, the period is 2 years or as per local approved labeling unless the participant has completed an accelerated drug elimination treatment.

[0461] A male participant must agree not to plan to father a child while enrolled in this study or within 90 days after the last dose of study intervention.

[0462] A male participant who has not had a vasectomy must agree to use a barrier method of birth control (eg, either wear a condom [with spermicidal foam / gel / film / cream / suppository if available in their locale] or a partner with an occlusive cap [diaphragm or cervical / vault caps] plus spermicidal foam / gel / film / cream / suppository if available in their locale), when engaging in any activity that allows for passage of ejaculate to a female of childbearing potential during the study and for 90 days after the last dose of study intervention. Male participants must also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak.

[0463] A male participant must agree not to donate or freeze sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention.

[0464] Note: the period of 90 days (in criteria #12, 13, and 14 above) applies to IL-23 RECEPTOR ANTAGONIST PEPTIDE. For participants receiving MTX, the period

[0465] (after the last administration of each drug) is 3 months or as per local approved labeling.

[0466] Informed Consent

[0467] Must sign an ICF indicating that the participant understands the purpose of. and procedures required for, the study and is willing to participate in the study.

[0468] Must sign a separate ICF if the participant agrees to provide the optional DNA sample for research (where local regulations permit). Refusal to give consent for the optional DNA research sample does not exclude a participant from participation in the study.

[0469] Is willing and able to adhere to the lifestyle restrictions specified in this protocol, including agreeing to avoid prolonged sun exposure and agree not to use tanning booths or other ultraviolet (UV) light sources during study (for participants with skin lesions).

[0470] Concomitant Therapy

[0471] Agree not to receive a live virus or live bacterial vaccination, including bacillus Calmette-Guerin (BCG) vaccination, during the study, or within 4 weeks after the last administration of study intervention.

[0472] Exclusion Criteria

[0473] Any potential participant who meets any of the following criteria will be excluded from participating in the study:

[0474] Medical Conditions

[0475] Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic (with the exception of PsA), psychiatric, genitourinary, or metabolic disturbances.

[0476] Currently has a malignancy or has a history of malignancy within 5 years prior to screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 12 weeks prior to the first study intervention administration or cervical carcinoma in situ that has been adequately treated with no evidence of recurrence for at least 12 weeks prior to the first study intervention administration).

[0477] Has known allergies, hypersensitivity, or intolerance to IL-23 RECEPTOR ANTAGONIST PEPTIDE or its excipients (refer to the IB).

[0478] Has unstable cardiovascular disease, defined as a clinical deterioration (eg, unstable angina, rapid atrial fibrillation, or transient ischemic attack) in the last 12 weeks prior to screening or a cardiac hospitalization within the last 12 weeks prior to screening.

[0479] Has other inflammatory diseases that might confound the evaluations of benefit of IL-23 RECEPTOR ANTAGONIST PEPTIDE therapy, including but not limited to RA, systemic lupus erythematosus, or Lyme disease (confirmed by Western blot).

[0480] Participants with fibromyalgia or osteoarthritis symptoms that, in the investigator’s opinion, would have potential to interfere with efficacy assessments.

[0481] Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance; or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly.

[0482] Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic non-remitting cystitis), severe fungal infection (eg, mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers.

[0483] Has a transplanted organ (with exception of a corneal transplant >12 weeks prior to the first administration of study intervention).

[0484] Has a history of an infected joint prosthesis or has ever received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.

[0485] Has or has had a herpes zoster infection within 8 weeks before screening.

[0486] Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular).

[0487] Has current drug-induced psoriasis (eg. a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium).

[0488] Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, active TB, nontuberculous mycobacterial infection, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis, HIV) or otherwise recurrent infections of abnormal frequency or prolonged duration, despite infection resolution, suggesting an immune-compromised status, as judged by the investigator.

[0489] Known active TB infection. IGRA TB test will be performed during screening. IGRA testing includes either QuantiFERON®-TB or T-SPOT® TB. a. Participants with history of active TB based on medical history will be excluded. b. Participants with a positive (or indeterminate) test result may participate in the study if further work up (according to local practice / guidelines) establishes conclusively that the participant has no evidence of active TB. If presence of latent TB is established, participants who are at low risk of reactivation, defined by local health authorities and investigator judgment, do not require prophylactic anti-tuberculosis treatment prior to or during the study. The decision to treat or not should be made by the treating physician / investigator. If the decision is made to treat the participant for latent TB, latent TB treatment must be initiated prior to the first administration of study intervention per local guidelines.

[0490] Has had major surgery (eg, requiring general anesthesia and hospitalization) within 8 weeks prior to screening, or will not have fully recovered from such surgery, or has such surgery planned during the time the participant is expected to participate in the study.

[0491] Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.

[0492] Have screening laboratory test results within the following parameters: a. Hemoglobin <8.5 g / dL (SI: <85 GPL)

[0493] White blood cells <3.5 x 10a / pL (SI: <3.5 GPL)

[0494] Neutrophils <1.5 x 103 / pL (SI: <1.5 GPL)

[0495] Platelets <100 x 103 / pL (SI: <100 GPL) eGFR <60 mL / min / 1.73m

[0496] Aspartate aminotransferase (AST), or alanine aminotransferase (ALT) >1.5 times the upper limit of normal range for the central laboratory conducting the test.

[0497] A one-time repeat of these screening laboratory tests is allowed during the

[0498] 5-week screening phase and the Investigator may consider the participant eligible if the previously abnormal laboratory test result is within acceptable the range on repeat testing in the central laboratory. No rescreening for ineligible ALT or AST is permitted.

[0499] Have positive rheumatoid factor OR anti-CCP antibodies at screening, according to the central laboratory criteria.

[0500] Previously received IL-23 RECEPTOR ANTAGONIST PEPTIDE

[0501]

[0502] Prior / Concurrent Clinical Study Experience

[0503] Received an investigational intervention or used an invasive investigational medical device within 90 days or 5 half-lives, whichever is longer, before the planned first dose of study intervention.

[0504] Diagnostic Assessments

[0505] All participants with:

[0506] Suicidal ideation in the 26 weeks prior to screening that may be defined as a C-SSRS rating of: Wish to be Dead, Non-Specific Active Suicidal Thoughts, or Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act and is considered to be at risk by the investigator.

[0507] Suicidal ideation or suicidal behavior in the 26 weeks prior to screening that may be defined as a C-SSRS rating of: Suicidal Ideation with Intention to Act. Suicidal Ideation with Specific Plan and Intent, Actual suicide attempt, Interrupted suicide attempt, Aborted suicide attempt, or Preparatory behaviors for making a suicide attempt, and is considered to be at risk by the investigator based on an evaluation by a mental health professional. The final decision on excluding a participant will be made at the judgment of the investigator.

[0508] Tested positive for or been exposed to COVID- 19 within 4 weeks prior to the first administration of study intervention.

[0509] Exceptions: Participants who have tested positive for or been exposed to COVID- 19 may participate if they have both an absence of symptoms and a negative validated COVID-19 test obtained at least 2 weeks after symptom onset (or the first positive test for asymptomatic infection) or exposure.

[0510] Follow local regulations for validated COVID-19 testing procedures and standard definition of COVID- 19 exposure. a) Tests positive for hepatitis B virus (HBV) infection (see Appendix 7) OR b) Is seropositive for antibodies to hepatitis C virus (HCV) at screening, unless the participant meets 1 of the following conditions: i. Has a history of successful treatment (defined as being negative for HCV RNA at least 12 weeks after completing antiviral treatment) and has a negative HCV RNA test result at screening, OR ii. While seropositive has a negative HCV RNA test result at least 12 weeks prior to screening and a negative HCV RNA test result at screening. c) Is infected with human immunodeficiency virus (HIV, a confirmed positive serology for HIV antibody).

[0511] Has a chest radiograph (or CT scan) within 12 weeks prior to the first study intervention that shows evidence of ongoing infection or malignancy.

[0512] Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments.

[0513] Has a history of drug or alcohol abuse according to DSM-5 criteria within 1 year before screening; use of marijuana is not exclusionary (if permitted by local regulations), unless deemed as abuse by the investigator.

[0514] Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria. then the participant must be excluded from participation in the study. Section 5.4, Screen

[0515] Failures, describes options for retesting. The required source documentation to support meeting the enrollment criteria are noted in Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.

[0516] Lifestyle Considerations Participants must be willing and able to adhere to the following lifestyle restrictions to be eligible for participation:

[0517] Prohibited and Restricted Therapies During the Study

[0518] Refer to Section 6.9 for details regarding prohibited and restricted therapy during the study. Refer to Sections 5.1 and 5.2 for allowed, restricted and prohibited concomitant medications and washout periods for prior medications.

[0519] It is recommended to be up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. It is strongly recommended that participants will have completed a locally-approved (or emergency use-authorized) COVID-19 vaccination regimen at least 2 weeks prior to study-related visits or procedures. Study participants should follow applicable local vaccine labeling, guidelines, and standards-of-care for participants receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrollment

[0520] Meals and Dietary Restrictions

[0521] The study intervention must be swallowed whole. Participants will be instructed to take the study intervention at approximately the same time every day upon waking with 240 mL (8 oz) water on an empty stomach (no food intake for at least 2 hours before and for at least 30 minutes after taking the study intervention).

[0522] Activity

[0523] Participants are encouraged to use sun protective measures (such as a hat, sunglasses, protective clothing, sunscreen) during study participation, as ultraviolet exposure may affect psoriasis efficacy assessments.

[0524] Agree to limit prolonged, direct sunlight exposure such as tanning in direct sunlight without sunscreen and avoid artificial sunlight (tanning beds or phototherapy).

[0525] Agree to abstain from excessive exercise (eg, body building, long distance running and cycling) 2-3 days prior to any study visit where chemistry laboratory blood samples are drawn.

[0526] Other Restrictions

[0527] For participants with nail psoriasis at baseline, agree to remove nail coverings prior to or at all visits where nail psoriasis is assessed.

[0528] Are willing to refrain from the use of complementary therapies for PsA or psoriasis including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medications and acupuncture within 2 weeks prior to the first study intervention administration and through Week 52.

[0529] Although the foregoing invention has been described in some detail by way of illustration and Example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate. Each aspect of the present invention defined in this or in any other section may incorporate definitions and limitations, such as those set forth throughout the originally filed disclosure, specification and claims.

Claims

1. CLAIMSWHAT IS CLAIMED IS:

1. A method for treating psoriatic arthritis in a subject in need thereof, comprising administering a compound of Formula (I):a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof; wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

2. The method of claim 1, wherein after the treatment, the subject further achieves a psoriatic arthritis measure of response determined by at least one criteria selected from the group consisting of a 50% improvement in the American College of Rheumatology core set disease index (ACR50), a 70% improvement in the American College of Rheumatology core set disease index (ACR70), Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C-reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI),Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and vdH-S score.

3. The method of claim 1, wherein after the treatment, the subject further achieves an improvement in a disease activity determined by at least one criteria selected from the group consisting of (i) improvement in disease activity as determined by the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75 / 90 / 100). (ii) an Investigator’s Global Assessment (IGA) Score of 0 / 1 and >2 grades improvement from baseline (among participants with baseline body surface area (BSA) >3% and with baseline IGA score >2), (iii) improvement in disease activity as determined by the American College of Rheumatology 50% and 70% improvement criteria (ACR50 / 70), (iv) change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), and (v) change from baseline in SF-36 physical component summary (PCS).

4. The method of any one of claims 1-3, wherein the subject achieves a statistically significant improvement in disease activity as determined by the Psoriasis Area and Severity Index 75 (PASI 75).

5. The method of any one of claims 1-3, wherein the subject achieves a statistically significant improvement in disease activity as determined by the Psoriasis Area and Severity Index 90 (PASI 90).

6. The method of any one of claims 1-3, wherein the subject achieves a psoriatic arthritis measure of response of about 100% reduction in PASI score compared to the baseline PASI score.

7. The method of any one of claims 1-3, wherein the subject further achieves Investigator’s Global Assessment (IGA) of 0 (clear) or 1 (minimal), or 2 or more grade reduction in the IGA, following a treatment period of at least about 24 weeks, wherein the subject has 3% or more body surface area (BSA) psoriatic involvement and an IGA score of 2 or more at the baseline before the treatment8. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 2 weeks after the beginning of treatment.

9. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 4 weeks after the beginning of treatment.

10. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 8 weeks after beginning of treatment.

11. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 16 weeks after beginning of treatment.

12. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 20 weeks after beginning of treatment.

13. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 24 weeks after beginning of treatment.

14. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 28 weeks after beginning of treatment.

15. 1'he method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 32 weeks after beginning of treatment.

16. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 40 weeks after beginning of treatment.

17. The method of any one of claims 1-3, wherein the psoriatic arthritis measure of response is measured at least 52 weeks after beginning of treatment.

18. The method of any one of claims 1-3, wherein the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is a hydrochloride salt of the compound of Formula (I) or solvate thereof.

19. The method of any one of claims 1-3, comprising orally administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof.

20. The method of any one of claims 1-3, comprising administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof daily.

21. The method of claim 20, comprising administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof in an amount of about 200 mg once daily.

22. The method of claim 20, comprising administering the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof in an amount of about 400 mg once daily.

23. The method of any one of claims 1-3, wherein the patient has a Body Surface Area (BSA) of at least 10% prior to treatment.

24. The method of any one of claims 1-3, wherein the patient has a PASI score of about 12 to 72 prior to treatment.

25. The method of any one of claims 1-3, wherein the subject has an Investigator’s Global Assessment (IGA) of at least 3 prior to treatment.

26. The method of any one of claims 1-3, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with a biologic agent for psoriatic arthritis.

27. The method of any one of claims 1-3, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with any IL-23 receptor antagonist for psoriatic arthritis.

28. The method of any one of claims 1-27, comprising orally administering to the subject, a pharmaceutical composition comprising a hydrochloride salt of a compound of Formula (I), wherein the amount of the compound of formula (I) in the hydrochloride salt is equivalent to about 200mg.

29. The method of claim 28, wherein the pharmaceutical composition comprises one or more excipients selected from the group consisting of colloidal anhydrous silica, silicified microcrystalline cellulose, crospovidone, and magnisum sterate,30. The method of claim 29, wherein the pharmaceutical composition comprises about 0.4% (w / w%) of colloidal anhydrous silica, about 74.1% (w / w%) of silicified microcrystalline cellulose, about 5.0 % (w / w%) crospovidone, and about 0.5% (w / w%) magnisum sterate.

31. The method of claim 29, wherein the pharmaceutical composition comprises about 4.0 mg of colloidal anhydrous silica, about 741 mg of silicified microcrystalline cellulose, about 50 mg crospovidone, and about 5 mg magnisum sterate.

32. The method of any one of claims 1-31, wherein the pharmaceutical composition further comprises a coating.

33. The method of claims 32, wherein the pharmaceutical composition further comprises about 30 mg coating.

34. The method of claim 32, wherein the pharmaceutical composition further comprises about 3% (w / w%) coating.

35. The method of claim 33 and 34, wherein the coating is Opadry QX 321A220063 Yellow coating.

36. The method of any one of claims 1-35, wherein the pharmaceutical composition is in a tablet form.

37. The method of any one of claims 28 to 36, wherein the subject takes the pharmaceutical composition after waking up in the morning before food intake and abstain from food intake for at least 30 minutes after administration of the pharmaceutical composition.

38. The method of any one of claims 28 to 37, wherein the subject takes the pharmaceutical composition with water.

39. The method of any one of claims 1-38, wherein the subject is at least 18 yearsold.

40. The method of any one of claims 1 to 39. wherein the subject has mild, moderate, or severe hepatic impairment.41 . The method of any one of claims 1 to 40, wherein the subject should not receive any live vaccine treatment during the administration of the pharmaceutical composition.

42. A method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a hydrochloride salt of the compound of Formula (I):to a patient in need thereof.

43. The method of claim 42, comprising administering a hydrochloride salt of the compound of formula (I) once daily, and wherein the amount of the compound of formula (I) in the hydrochloride salt is equivalent to about 200 mg.

44. The method of clam 42 or 43, wherein the hydrochloride salt of the compound of Formula (I) is in a crystalline form.

45. The method of any one of claims 42 to 44, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

46. The method of any one of claims 42 to 45, wherein after the treatment, the subject further achieves a psoriatic arthritis measure of response determined by at least one criteria selected from the group consisting of a 50% improvement in the American College of Rheumatology core set disease index (ACR50), a 70% improvement in the American Collegeof Rheumatology core set disease index (ACR70), Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C-reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDA1), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and vdH-S score.

47. The method of any one of claims 42 to 46, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with a biologic agent for psoriatic arthritis.

48. The method of any one of claims 42 to 47, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, the subject has not been treated with any IL-23 receptor antagonist for psoriatic arthritis.

49. A method of treating a patient population diagnosed with psoriatic arthritis, comprising orally administering a hydrochloride salt of the compound of Formula (I):to said patient population, wherein the amount of the compound of formula (I) in thehydrochloride salt is equivalent to about 400 mg.

50. The method of claim 49, wherein the method comprises administering the hydrochloride salt of compound of Formula (I) once daily.51 . The method of claim 49 or 50, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.

52. 1'he method of any one of claims 49 to 51, wherein after the treatment, the subject further achieves a psoriatic arthritis measure of response determined by at least one criteria selected from the group consisting of a 50% improvement in the American College of Rheumatology core set disease index (ACR50), a 70% improvement in the American College of Rheumatology core set disease index (ACR70), Health Assessment Questionnaire Disability Index (HAQ-DI), Investigator’s Global Assessment (IGA), Disease Activity Score 28 (DAS28) C-reactive protein (CRP), resolution of enthesitis, resolution of dactylitis, Leeds enthesitis index (LEI), dactylitis assessment score, Short Form Health survey (SF-36) in the mental and physical component summary (MCS and PCS), achievement of minimal disease activity (MDA), very low disease activity (VLDA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), GRAppa Composite score (GRACE), Psoriatic Arthritis Disease Activity Score (PASDAS), modified Composite Psoriatic Disease Activity Index (mCPDAI), Psoriatic Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Functional Assessment of Chronic Illness Therapy (FACIT), a Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and vdH-S score.

53. The method of any one of claims 49 to 52, wherein the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof is a hydrochloride salt of the compound of Formula (I) or solvate thereof.

54. The method of any one of claims 49 to 53, wherein a patient in the patient population has an active psoriatic arthritis.

55. The method of any one of claims 49 to 54, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, a patient in the patient population has not been treated with a biologic agent for psoriatic arthritis.

56. The method of any one of claims 49 to 55, wherein, before the start of treatment with the compound of Formula (I) or pharmaceutically acceptable salt or solvate thereof, a patient in the patient population has not been treated with any IL-23 receptor antagonist for psoriatic arthritis.

57. The method of c any one of claims 49 to 56, wherein the subject is a patient.

58. The method of any one of claims 49 to 57, wherein the subject is an adult patient or adolescent patient that is between 12 and 18 years old.

59. A method for treating psoriatic arthritis in a subject in need thereof, comprising orally administering a pharmaceutical composition comprising a hydrochloride salt of a compound of Formula (I):and one or more excipients selected from the group consisting of colloidal anhydrous silica, silicified microcrystalline cellulose, crospovidone, and magnisum sterate, wherein the amount of the compound of formula (1) in the hydrochloride salt is equivalent to about 200mg, and wherein the pharmaceutical composition is administered once daily.

60. The method of claim 59, wherein the subject achieves a psoriatic arthritis measure of response at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after the treatment.61 . The method of claim 59 or 60, wherein the pharmaceutical composition comprises about 4.0 mg of colloidal anhydrous silica, about 741 mg of silicified microcrystalline cellulose, about 50 mg crospovidone, and about 5 mg magnisum sterate.

62. The method of any one of claims 59-61, wherein the pharmaceutical composition further comprises a coating.

63. The method of any one of claims 59-62, wherein the pharmaceutical composition further comprises about 30 mg coating.

64. The method of claim 62 or 63, wherein the coating is Opadry QX321A220063 Yellow coating.

65. The method of any one of claims 59-64, wherein the pharmaceutical composition is in a tablet form.

66. The method of any one of claims 59 to 65, wherein the subject takes the pharmaceutical composition after waking up in the morning before food intake and abstain from food intake for at least 30 minutes after administration of the pharmaceutical composition.

67. The method of any one of claims 59 to 66, wherein the subject takes the pharmaceutical composition with water only.

68. The method of any one of claims 59 to 67, wherein the subject is at least 12 years old.

69. The method of any one of claims 59 to 68, wherein the subject has mild, moderate, or severe hepatic impairment.

70. The method of any one of claims 59 to 69, wherein the subject should not receive any live vaccine treatment during the administration of the pharmaceutical composition.

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