Method for treating IgA nephropathy using TACI-Fc fusion protein

Abstract

The present invention relates to a therapeutic agent for IgA nephropathy using TACI-Fc fusion protein, its dosage scheme, administration interval and administration method. The results showed that the urinary protein level of patients in the treatment group was significantly reduced compared to baseline, and the difference was statistically significant when compared to the placebo group. There were also significant differences between the treatment group and the placebo control group in several secondary endpoints of the clinical trial.

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical agent, a dosage scheme, a dosage interval and a method of administration for treating IgA nephropathy. [Background technology]

[0002] IgA nephropathy (i.e. immunoglobulin a nephropathy, IgA nephropathy, IgAN) is glomerulonephritis caused by immune complexes, manifesting as hematuria, proteinuria and various degrees of progressive renal failure. The pathogenesis of this disease is very complex, and it is believed that genetic, environmental and immune factors jointly determine the occurrence of IgA nephropathy, but it is mainly believed that various factors cause excessive deposition of abnormally glycosylated poly IgA1 molecules in the mesangium of the kidney, which induces mesangial inflammatory responses and excessive activation of complement, thereby progressing the disease. Patients eventually develop renal failure or end-stage renal disease, and about 50% of patients require dialysis or kidney transplantation. According to Frost & Sullivan, the number of patients with IgA nephropathy worldwide increased from 8.8 million in 2015 to 9.3 million in 2020 (including 2.2 million in China). The total number of IgA nephropathy patients worldwide is estimated to reach 9.7 million (including 2.3 million in China) in 2025 and 10.2 million (including 2.4 million in China) in 2030. Therefore, there is a huge clinical need in the field of IgA nephropathy treatment worldwide.

[0003] However, there are still no approved effective treatments or biological agents for IgA nephropathy worldwide. The current standard of care is blockade of the renal-angiotensin-aldosterone system and immunosuppression, including steroids, which are often associated with severe toxic side effects. As of July 20, 2021, there are only 11 new biological agents in clinical investigation for IgA nephropathy worldwide (see Table 1).

[0004] [Table 1] Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, there is huge clinical need in the field of IgA nephropathy treatment, whether in China or worldwide. [Means for solving the problem]

[0006] Detailed analysis of clinical data shows that the TACI-Fc fusion protein provided by the present invention has a significant technical effect in treating cancer patients with IgA nephropathy. Specifically, the present invention provides a method for treating IgA nephropathy, comprising administering a therapeutically effective amount of a TACI-Fc fusion protein to a patient suffering from IgA nephropathy. (i) the extracellular domain of TACI or a fragment thereof that binds to Blys and / or APRIL; (ii) a human immunoglobulin constant region.

[0007] Furthermore, the TACI extracellular domain or a fragment thereof that binds to Blys and / or APRIL comprises the amino acid sequence shown in SEQ ID NO:1. JPEG0007644838000002.jpg23170

[0008] Furthermore, the constant region of the human immunoglobulin comprises an amino acid sequence as set forth in SEQ ID NO:2 or an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity to SEQ ID NO:2. JPEG0007644838000003.jpg38170

[0009] Additionally, the constant region of said human immunoglobulin comprises an amino acid modification corresponding to one or more of sites 3, 8, 14, 15, 17, 110, 111 and 173 of SEQ ID NO: 2. The modification is preferably an amino acid substitution, deletion or insertion.

[0010] Further, said substitutions are selected from the group consisting of P3T, L8P, L14A, L15E, G17A, A110S, P111S and A173T. Furthermore, the constant region of said human immunoglobulin comprises the amino acid sequence shown in SEQ ID NO:3. JPEG0007644838000004.jpg38170

[0011] Furthermore, said human immunoglobulin is IgG1.

[0012] Furthermore, the TACI-Fc fusion protein has the amino acid sequence shown in SEQ ID NO:4. JPEG0007644838000005.jpg54170

[0013] Further, the TACI-Fc fusion protein is Telitaccept.

[0014] Further, the TACI-Fc fusion protein is administered in an amount ranging from 160 to 240 mg per administration. In some specific embodiments, the TACI-Fc fusion protein is administered in an amount of 160 mg per administration. In other specific embodiments, the TACI-Fc fusion protein is administered in an amount of 240 mg per administration.

[0015] Furthermore, the TACI-Fc fusion protein is used 2 to 4 times per month.

[0016] Furthermore, the TACI-Fc fusion protein is administered continuously for about 2 to 50 weeks.

[0017] Furthermore, the TACI-Fc fusion protein may be administered subcutaneously, intramuscularly, orally, or intravenously.

[0018] Furthermore, the IgA nephropathy is primary IgA nephropathy.

[0019] Further, the patient may be an adult patient or a pediatric patient.

[0020] The present invention also relates to a method for treating IgA nephropathy comprising administering to a patient a pharmaceutical composition comprising a TACI-Fc fusion protein, wherein said pharmaceutical composition further comprises a pharma- ceutically acceptable carrier.

[0021] The present invention also relates to the use of a TACI-Fc fusion protein in the preparation of a medicament for treating patients with IgA nephropathy.

[0022] Results of clinical studies conducted on the present invention showed that patients in the telitacicept treatment group had a significant reduction in urinary protein levels compared to baseline, and the difference was statistically significant compared to the placebo group. There were also significant differences between the treatment group and the placebo control group in several secondary endpoints of the clinical trial. [Brief description of the drawings]

[0023] [Figure 1] Figure 1 shows the change in eGFR over time. [Diagram 2] FIG. 2 shows the time course of UACR. [Diagram 3] FIG. 3 shows the time course of urinary red blood cell counts. [Figure 4] FIG. 4 shows the time course of IgA levels. [Diagram 5] FIG. 5 shows the change in IgG levels over time. [Figure 6] FIG. 6 shows the time course of IgM levels. [Figure 7] FIG. 7 shows the time course of B lymphocyte (CD19+) counts. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Unless otherwise defined, technical and scientific terms used herein have the same meaning as understood by one of ordinary skill in the art. For definitions and terms in this field, those skilled in the art can refer specifically to Current Protocols in Molecular Biology (Ausubel).

[0025] The present invention provides the use of a TACI-Fc fusion protein (also referred to as a "TACI-immunoglobulin fusion protein" and may be used interchangeably herein) in the treatment of IgA nephropathy. The patient according to the present invention is preferably a mammal, such as a human, and more preferably an adult or a child.

[0026] The TACI-immunoglobulin fusion protein provided by the present invention comprises 1) a polypeptide comprising a domain at least partially identical to the TACI extracellular domain or a fragment thereof capable of binding to BlyS and / or APRIL, and 2) a constant region of a human immunoglobulin. U.S. Patent Nos. 5,969,102, 6,316,222 and 6,500,428, and U.S. Application Nos. 09 / 569,245 and 09 / 627,206, the contents of which are incorporated herein by reference, describe the extracellular domain of TACI and certain fragments of the TACI extracellular domain capable of interacting with TACI ligands, including BlyS and APRIL. A Chinese patent with publication number CN101323643A describes a TACI-Fc fusion protein comprising a fragment of amino acids 13-118 of the TACI extracellular domain.

[0027] The term "TACI" in the present invention, i.e., transmembrane activator and calcium regulating ligand interactor, is known as a member of the tumor necrosis factor receptor superfamily. The term "BLys" in the present invention refers to B lymphocyte stimulator, which is a member of the TNF ligand superfamily that exists in two forms, membrane-bound and soluble, and is specifically expressed on the surface of bone marrow cells, and selectively stimulates the proliferation of B lymphocytes and the production of immunoglobulins. The term "APRIL" (a proliferation-inducing ligand) in the present invention is a tumor necrosis factor (TNF) analogue that can stimulate the proliferation of primitive B cells and T cells in the body, promote the accumulation of B cells, and increase the content in the spleen. APRIL can specifically bind to TACI and BCMA, and upon binding, it can block APRIL from binding to B cells and suppress the proliferation response of primitive B cells stimulated by APRIL. APRIL can also compete with BLys for binding to receptors (BCMA, TACI).

[0028] The term "immunoglobulin" in the present invention refers to an animal protein having antibody activity, preferably a human immunoglobulin. In some embodiments, the "immunoglobulin" may be IgG, IgM, IgE, IgD or IgA, preferably IgG, more preferably IgG1 or IgG4.

[0029] The term "human immunoglobulin constant region" in the present invention particularly refers to the heavy chain constant region of human immunoglobulin. In one embodiment, the "human immunoglobulin constant region" is a complete human immunoglobulin heavy chain constant region. In another specific embodiment, the "human immunoglobulin constant region" is a fragment having a partial amino acid sequence of the "complete human immunoglobulin heavy chain constant region", i.e., a "fragment of the human immunoglobulin heavy chain constant region". Taking human immunoglobulin IgG1 as an example, the "complete human immunoglobulin heavy chain constant region" includes a CH1 domain, a hinge region, a CH2 domain, and a CH3 domain. A "fragment of a heavy chain constant region of a human immunoglobulin" may have a combination of various structures, for example, but not limited to, a complete or partial amino acid sequence of a CH1 domain, a complete or partial amino acid sequence of a hinge region, a complete or partial amino acid sequence of a CH2 domain, a complete or partial amino acid sequence of a CH3 domain, a complete or partial amino acid sequence of a CH1 domain and a complete or partial amino acid sequence of a hinge region, a complete or partial amino acid sequence of a CH1 domain and a complete or partial amino acid sequence of a CH2 domain, a complete or partial amino acid sequence of a CH1 domain and a complete or partial amino acid sequence of a CH3 domain, a complete or partial amino acid sequence of a hinge region and a CH2 domain, These include a complete or partial amino acid sequence of the hinge region and a complete or partial amino acid sequence of the CH3 domain, a complete or partial amino acid sequence of the CH2 domain and a complete or partial amino acid sequence of the CH3 domain, a complete or partial amino acid sequence of the CH1 domain, a complete or partial amino acid sequence of the hinge region and a complete or partial amino acid sequence of the CH2 domain, a complete or partial amino acid sequence of the CH1 domain, a complete or partial amino acid sequence of the hinge region and a complete or partial amino acid sequence of the CH3 domain, and a complete or partial amino acid sequence of the hinge region, a complete or partial amino acid sequence of the CH2 domain and a complete or partial amino acid sequence of the CH3 domain.In some preferred embodiments of the present invention, the "constant region of human immunoglobulin" particularly refers to a fragment of the heavy chain constant region of human immunoglobulin, and preferably includes a partial amino acid sequence of the hinge region, the complete amino acid sequence of the CH2 domain, and the complete amino acid sequence of the CH3 domain. In some preferred embodiments, the "constant region of human immunoglobulin" according to the present invention includes, for example, the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 3, or a sequence identical thereto.

[0030] In the TACI-immunoglobulin fusion protein provided by the present invention, the immunoglobulin portion is preferably IgG1. In the present invention, the IgG1 heavy chain constant region is preferably an IgG1 Fc fragment containing the CH2 and CH3 regions, and may be a wild-type IgG1 Fc fragment or a mutated IgG1 Fc fragment.

[0031] In another alternative embodiment, the constant regions of the immunoglobulins provided herein can have one or more amino acid changes introduced therein, such as substitutions (i.e., mutations), additions (i.e., insertions) or deletions (i.e., deletions).

[0032] The term "therapeutically effective amount" in the present invention refers to the commonly used dose of a drug, which is the effective dose range commonly used in clinical practice, and is generally between the minimum effective amount and the maximum dose. The minimum effective amount refers to the minimum dose that can cause a pharmacological effect of a drug. The maximum dose refers to the maximum therapeutic amount, i.e., the limit of safe drug use, and if the maximum dose is exceeded, poisoning may occur.

[0033] The term "telitacicept" in the present invention (also called "Tai Ai" in Chinese, which can be used interchangeably in the present invention) is a TACI-Fc fusion protein, whose INN name is Telitaccept, and whose amino acid sequence is shown in SEQ ID NO: 4, or see https: / / extranet.who.int / soinn / mod / page / view.php?id=137&inn_n=10932.

[0034] The three-letter code and one-letter code of amino acids used in the present invention are as described in J. biol. chem, 243, p3558 (1968). There are various methods for numbering amino acid sites, such as Kabat numbering, EU numbering, and sequential numbering, but in the present invention, the "sequential numbering" method is adopted as the method for numbering amino acid sites. For example, "sites 3, 8, 14, 15, 17, 110, 111, or 173 of SEQ ID NO: 2" in the present invention refers to the third amino acid, the eighth amino acid, etc. of SEQ ID NO: 2. In the present invention, "P3T" means that the third amino acid sequence of SEQ ID NO: 2 is mutated from the original "P" to "T". In addition, "L8P" means that the eighth amino acid sequence of SEQ ID NO: 2 is mutated from the original "L" to "P". Let us analogize as in this example.

[0035] The term "pharmaceutical composition" of the present invention refers specifically to a formulation comprising a TACI-Fc fusion protein and can be in a variety of forms, for example, an injectable liquid solution or suspension, a pre-injection solid form of a solution or suspension suitable for dissolution in a liquid carrier (e.g., a lyophilized composition for reconstitution in sterile water containing a preservative), prepared for topical administration, for example, as an ointment, cream or powder, prepared for oral administration, as a tablet, capsule, spray, or syrup (optionally flavored). Typically, it can be prepared as an injectable liquid solution or suspension, or a pre-injection solid form of a solution or suspension suitable for dissolution in a liquid carrier.

[0036] The TACI-Fc fusion proteins or pharmaceutical compositions of the invention can be administered via any route, including, but not limited to, oral administration, intravenous injection, intramuscular injection, intraarterial injection, intramedullary injection, intraperitoneal injection, intramedullary injection, intracardiac, transdermal, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes.

[0037] The TACI-Fc fusion protein or pharmaceutical composition thereof provided by the present invention may be prepared and stored in the form of a lyophilized, sterile, or solution. The term "treatment" in the present invention refers to a given disease or condition. "Treatment" includes, but is not limited to, suppression of the disease or condition so as to prevent the progression of the disease or condition, alleviation of the disease or condition so as to cause regression of the disease or condition, or alleviation of symptoms caused by the disease or condition so as to alleviate, prevent, or treat the symptoms of the disease or condition. EXAMPLES

[0038] Hereinafter, the embodiments of the present invention will be described in detail in conjunction with examples. However, those skilled in the art will understand that the following examples are used to explain the present invention and should not be considered as limiting the scope of the present invention.

[0039] Example 1: Phase II Clinical Trial of Treating Patients with IgA Nephropathy with Teritacicept

[0040] 1. Personnel selection criteria 1) IgA nephropathy was diagnosed by pathological biopsy.

[0041] 2) Male or female aged 18 to 70 years

[0042] 3) During the screening period, 24-hour urinary protein was ≥ 0.75g / 24h at least once during Visit 1 and Visit 2, and 24-hour urinary protein was ≥ 0.75g / 24h at Visit 3.

[0043] 4) Measured glomerular filtration rate or estimated GFR (using the CKD-EPI formula) of 35 mL / min per 1.73 m 2 Beyond

[0044] 5) Subjects were receiving a baseline treatment regimen including an ACEI / ARB for 12 weeks prior to randomization, and the dose of the ACEI / ARB (within the maximum tolerated range) was stable within 4 weeks prior to randomization.

[0045] 2. Test group division [Table 2]

[0046] [Table 3]

[0047] 3. End Point Indicator [Table 4]

[0048] [Table 5]

[0049] 4. Statistical methods and analytical data sets Continuous variables were described as mean, standard deviation, median, minimum, and maximum values, and count and graded data were described as frequency counts and percentages. All statistical tests were two-sided, and differences were considered statistically significant when p was less than or equal to 0.05 (p ≤ 0.05). Two data sets were used for treatment efficacy analysis: the full analysis set (FAS) and the per protocol set (PPS), and the data set for safety analysis was the safety analysis set (SS).

[0050] The full analysis set (FAS) of this study included a total of 44 subjects: 14 in the placebo group, 16 in the teritacicept 160 mg group, and 14 in the teritacicept 240 mg group. Safety analysis set (SS) data were the same as the FAS population. The per protocol set (PPS) included 42 subjects in total, excluding 2 subjects in the placebo group who spontaneously withdrew: 12 in the placebo group, 16 in the teritacicept 160 mg group, and 14 in the teritacicept 240 mg group.

[0051] 5. Main results (1) Analysis of indicators of main treatment effect After 24 weeks of treatment, subjects in the placebo group had essentially no change in mean 24-hour urinary protein levels, with a decrease of 0.03 g / 24h (2.62%), subjects in the telitacicept 240 mg group had a decrease of 0.89 g / 24h (49.29%) in mean urinary protein from pre- to post-dose, and subjects in the telitacicept 160 mg group had a decrease of 0.32 g / 24h (24.71%) in mean urinary protein from pre- to post-dose. Thirteen subjects (92.86%) in the telitacicept 240 mg group had a decrease in 24-hour urinary protein from baseline levels, with three subjects experiencing the greatest decrease, 1.89 g / 24h, 1.77 g / 24h, and 1.54 g / 24h, respectively. In the telitacicept 160 mg group, 11 subjects (68.75%) had a decrease in 24-hour urinary protein compared to baseline levels after 24 weeks of medication, with one subject experiencing the greatest decrease, with a 24-hour urinary protein decrease of 1.40 g / 24h compared to baseline.

[0052] (2) Analysis of secondary treatment effect indicators A. Time course analysis of estimated glomerular filtration rate (eGFR) After 24 weeks of treatment, subjects in the 160 mg and 240 mg teritacicept groups had mean estimated glomerular filtration rates (eGFR) of 4.32 mL / min / 1.73 m, respectively. 2 and 2.33mL / min / 1.73m 2 The placebo group had a mean level of 5.70 mL / min / 1.73 m 2 Analysis of variance (ANOVA) showed that the differences in changes in eGFR between subjects in the telitacicept 160 mg and 240 mg groups compared to the placebo group were statistically significant, with p values ​​of 0.002 and 0.015, respectively. The changes in eGFR over time for subjects in each group are shown in Figure 1.

[0053] B. Temporal analysis of urinary albumin / creatinine ratio (UACR) In this study, UACR was collected as selective data, and UACR data was collected for a total of 37 subjects (13 in the placebo group, 14 in the 160 mg teritacicept group, and 10 in the 240 mg teritacicept group). As shown in Figure 2, the two teritacicept treatment groups showed a sustained decrease in mean UACR levels during the treatment period. ANOVA analysis confirmed that the difference between the decrease in UACR in subjects in the two teritacicept treatment groups and the change in UACR in placebo subjects was statistically significant (p≦0.05). There was a statistical difference in the change in 24-hour urinary protein between subjects in the two teritacicept treatment groups and subjects in the placebo group at weeks 12, 16, and 20 of treatment. Compared to baseline levels, after 24 weeks of treatment, subjects in the 160 mg and 240 mg telitacicept groups had mean UACR reductions of 347.81 mg / g and 627.55 mg / g, respectively, and subjects in the placebo group had mean UACR reductions of 16.77 mg / g.

[0054] C. Serial analysis of urinary red blood cell counts There was almost no change in the number of red blood cells in urine in each group before and after administration of the drug. The results of the ANOVA analysis showed that there was no statistically significant difference in the changes in red blood cells in urine among the subjects of each group. The changes in the red blood cell count in urine over time for the subjects of each group are shown in Figure 3.

[0055] D. Time course analysis of immunoglobulin A (IgA) The teritacicept groups experienced a continuous decline in subjects' immunoglobulin A (IgA) levels from the start of dosing through week 24 of dosing. Beginning at week 8 of dosing, the difference in subjects' immunoglobulin A (IgA) between the two teritacicept treatment groups and the placebo group became statistically significant, p<0.001, and continued in this manner through week 24 of dosing. Compared to baseline, after 24 weeks of dosing, the mean IgA levels of subjects in the placebo group changed only slightly, showing a decrease of 0.01 g / L (decrease rate of 1.11%), while the mean IgA levels of subjects in the teritacicept 160 mg group decreased by 1.48 g / L (45.75%) and the mean IgA levels of subjects in the teritacicept 240 mg group decreased by 1.17 g / L (15.83%). The time course of mean IgA levels in each group of subjects is shown in FIG.

[0056] E. Time course analysis of immunoglobulin G (IgG) After dosing, subjects in the teritacicept groups had a continuous decline in immunoglobulin G (IgG) levels. ANOVA analysis showed that the difference in immunoglobulin G (IgG) changes between the two teritacicept groups compared to the placebo group became statistically significant from the 4th week, p<0.001, and continued in this manner until the 24th week of dosing. After 24 weeks of dosing, compared to baseline, subjects in the placebo group had little change in IgG levels, with a mean increase of 0.10 g / L (0.22%), subjects in the teritacicept 160 mg group had a decrease of 3.00 g / L (26.16%), and subjects in the teritacicept 240 mg group had a decrease of 2.56 g / L (24.55%). The change over time in the mean IgA levels of subjects in each group is shown in Figure 5.

[0057] F. Time course analysis of immunoglobulin M (IgM) Subjects receiving telitacicept experienced a continuous decline in immunoglobulin M (IgM) levels from the start of treatment. A statistically significant difference in change between telitacicept and placebo persisted from week 8 through week 24. Compared to baseline levels, subjects receiving placebo experienced an increase of 0.03 g / L (0.63%) at week 24. Subjects receiving 160 mg telitacicept experienced a decline in mean IgM levels of 0.76 g / L (64.28%), and subjects receiving 240 mg telitacicept experienced a decline in mean levels of 0.62 g / L (65.34%). Statistical analysis showed that the difference in IgM changes between the two telitacicept treatment groups and the placebo group became statistically significant (p<0.001) from week 8 onwards, and this statistical difference persisted until week 24. The mean IgA levels over time for subjects in each group are shown in Figure 6.

[0058] GB lymphocytes (CD19 + ) Time-course analysis of counts After 24 weeks of treatment, the placebo group had a significantly higher mean B lymphocyte (CD19 + ) levels in subjects in the 160 mg telitacicept group were reduced by 0.32 cells / μl (1.18%), and the mean B lymphocyte (CD19 + ) decreased by 108.36 cells / μl (26.23%), and the mean B lymphocyte (CD19 + ) decreased by 36.72 cells / μL (21.40%). Throughout the study, the telitacicept 240 mg group compared with the placebo group, and the B lymphocyte (CD19 + The differences between groups were not statistically significant (p>0.05). At weeks 20 and 24, when comparing subjects in the telitacicept 160 mg group with placebo, subjects' B lymphocyte (CD19 + The differences between groups were statistically significant (p≦0.05). Specific changes are shown in FIG. 7.

[0059] H. Safety Assessment This study demonstrated that telitacicept has a favorable safety profile in the treatment of patients with IgA nephropathy. There were no deaths or discontinuations due to adverse events (AEs) during the study, and all subjects, except for two subjects who withdrew early for personal reasons (not being able to receive the treatment as planned), completed the treatment as scheduled. The differences in the incidence of adverse events (TEAEs), serious adverse events (SAEs), and serious adverse reactions (SADRs) between the groups were not statistically significant (P>0.05). The differences in the incidence of ADRs between the groups were statistically significant (p<0.05). However, adverse reactions (ADRs) in subjects in the medication group were mainly injection site reactions, and were of grade 3 or less in severity.

[0060] Thus, the study data showed that after 24 weeks of treatment, subjects in the teritacicept 240 mg and 160 mg groups had a reduction in 24-hour urinary protein levels from baseline. Subjects in the teritacicept 240 mg group had a reduction in mean 24-hour urinary protein of 0.89 g / 24h (49.29%), and subjects in the teritacicept 160 mg group had a reduction in mean 24-hour urinary protein of 0.32 g / 24h (24.71%). From weeks 16 to 24 of treatment, the difference in reduction in subjects' urinary protein levels was statistically significant for the teritacicept 240 mg group compared to placebo subjects. From weeks 16 to 20 of treatment, the difference in reduction in subjects' 24-hour urinary protein levels was statistically significant for the teritacicept 160 mg group compared to placebo subjects. Before and after dosing, subjects in both telitacicept groups showed an increase in the mean long-term renal indicators, estimated glomerular filtration rate (eGFR), and a significant decrease in the mean levels of immunoglobulins (IgA, IgG, and IgM). When compared to the placebo group, the differences in the changes in the above indicators between the groups were also statistically significant. However, until now, there has not yet been a drug approved as a targeted treatment for IgA nephropathy, so a horizontal comparison using clinical data from positive drugs has not been possible. However, the results obtained in this study are superior to the clinical trial data of most IgA drugs from the same period. Therefore, this study demonstrated that telitacicept 240 mg / week and telitacicept 160 mg / week are effective in treating IgA nephropathy.

[0061] Data from this study also demonstrated that telitacicept had a favorable safety profile during the treatment of IgA nephropathy: There were no serious adverse events, withdrawals due to adverse events, or deaths during the study.

[0062] The above results showed that the urinary protein levels of patients in the telitacicept treatment group were significantly lower than baseline, and the difference was statistically significant when compared to the placebo group. In addition, there were significant differences between the treatment group and the placebo control group in several secondary endpoints of the clinical trial. In view of the above results and analysis, this study demonstrated that telitacicept (240 mg / week) and telitacicept (160 mg / week) have efficacy and good safety during the treatment of IgA nephropathy.

[0063] It should be noted that the above description is merely a preferred embodiment, and is used only as an example, and does not limit the combination of features necessary to implement the present invention. The titles provided are not meant to limit the various embodiments of the present invention. Terms such as "contain", "include" and "include" are not meant to limit. Furthermore, unless otherwise specified, if a noun is not modified by a number, its plural is included. The term "or" means "and / or". Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art.

[0064] All publications and patents mentioned in this specification are incorporated herein by reference. Various modifications and variations made to the methods and combinations described in this invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described through specific preferred embodiments, it should be understood that the invention for which protection is sought should not be unduly limited to these specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that become apparent to those skilled in the art are intended to be encompassed within the scope of the claims of this application.

Claims

1. A pharmaceutical composition for treating IgA nephropathy, comprising a TACI-Fc fusion protein having the amino acid sequence shown in SEQ ID NO:

4.

2. The pharmaceutical composition for treatment according to claim 1, characterized in that the TACI-Fc fusion protein is Telitaccept.

3. The pharmaceutical composition for treatment according to claim 1 or 2, characterized in that the TACI-Fc fusion protein is administered in a dosage range of 160-240 mg each time.

4. A pharmaceutical composition for the treatment described in claim 1 or 2, characterized in that the TACI-Fc fusion protein is administered at a dosage of 160 mg or 240 mg each time.

5. The pharmaceutical composition for treatment according to claim 1 or 2, characterized in that the TACI-Fc fusion protein is administered 2-4 times per month and / or continuously for about 2-50 weeks.

6. The pharmaceutical composition for treatment according to claim 1 or 2, characterized in that the TACI-Fc fusion protein is administered by subcutaneous injection, intramuscular injection, oral or intravenous administration route.

7. The pharmaceutical composition for treatment according to claim 1, characterized in that the IgA nephropathy is primary IgA nephropathy.

8. Use of a TACI-Fc fusion protein having the amino acid sequence shown in SEQ ID NO: 4 in the preparation of a medicament for treating a patient with IgA nephropathy.

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