A Study of Telitacicept in Patients with Primary Immunoglobulin A（IgA） Nephropathy

The purpose of this study is to evaluate the efficacy and safety of Telitacicept in patients with primary IgA nephropathy at risk of progressing to end-stage renal disease(ESRD), despite maximum tolerated treatment with renin-angiotensin system(RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).

This study consists of a 5-week screening period, a double-blind treatment period divided into phase A and phase B. Eligible subjects will be randomly assigned in a 1:1 ratio to receive either Telitacicept 240mg or placebo. Subjects will be given subcutaneous injection（SC） Telitacicept or placebo once a week for a total of 39 doses in phase A and once every 2 weeks for a total of 32 doses in phase B.

Primary endpoint of phase A will be measured at week 39. Primary endpoint of phase B will be measured at week 104.

Eligibility Criteria:
Inclusion Criteria:

1. Voluntary informed consent provided;
2. Male or female aged ≥ 18 years old;
3. IgA nephropathy confirmed by pathological biopsy;
4. During the screening period, UPCR ≥ 0.8 g/g or 24-hour urine protein ≥ 1.0 g/day based on 24-hour urine collection at Visit 1 and/or Visit 2 and at Visit 3;
5. eGFR ≥ 30 mL/min per 1.73 m\^2 (using the CKD-EPI);
6. Have been on a treatment regimen including ACEI/ARB for 12 weeks and on a stable use of ACEI/ARB medication at the maximum tolerated dose/maximum allowable dose within 4 weeks prior to randomization. Subjects who use both ACEIs and ARBs will be excluded.

Exclusion Criteria:

1. Clinically significant abnormal laboratory tests;
2. Secondary IgA nephropathy;
3. Other types of glomerular disease such as crescentic glomerulonephritis（\>50%）, minimal change nephropathy with IgA deposition;
4. Renal transplant;
5. Cirrhosis, as assessed by the investigator;
6. Experienced any of the following cardiovascular and cerebrovascular events within 24 weeks prior to randomization: myocardial infarction, unstable angina, ventricular arrhythmia, New York Heart Association（NYHA） Class II or higher heart failure, stroke, etc.;
7. Sitting position SBP\>140 mmHg or DBP\>90 mmHg for at least once at 2 visits during the screening period;
8. Poorly controlled type 1 and type 2 diabetes (glycated hemoglobin A1c\[HbA1c\]\>8% or 64mmol/mol);
9. Received immunosuppressants within 12 weeks prior to randomization, including but not limited to cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii;
10. Received anti-CD20 therapy (for example, Rituximab Injection) within 24 weeks prior to randomization;
11. Received systemic glucocorticoid treatment within 12 weeks prior to randomization, excluding the followings: ① received systemic treatment with prednisolone ≤ 0.5mg/kg or equivalent glucocorticoid for non- IgA nephropathy for no more than 3 courses (≤ 2 weeks per course) in the past 52 weeks; ② topical administration or nasal inhalation;
12. Hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization;
13. Active tuberculosis and untreated latent tuberculosis;
14. Hepatitis B: patients with active hepatitis (patients with positive HBsAg) or latent hepatitis B (patients with positive HBcAb and positive HBV-DNA);
15. Hepatitis C;
16. Patients with HIV;
17. Malignancy within the past 5 years, except for treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, colon polyps, or cervical cancer in situ;
18. Pregnant women, lactating women, and subjects with childbearing plans during the trial;
19. Allergic to biological products of human origin;
20. Received any investigational therapy within 4 weeks or within 5 times the half-life of the investigational product (whichever is longer) prior to randomization;
21. Received live vaccination within 4 weeks prior to randomization;
22. Drug or alcohol abuse/dependence within 52 weeks prior to randomization;
23. Not suitable for the study in the opinion of the investigator.