A Study of Telitacicept for IgA Nephropathy (TELIGAN)

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.

Inclusion criteria

• Voluntary informed consent provided;
• Male or female aged ≥ 18 years old;
• IgA nephropathy confirmed by pathological biopsy;
• 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;
• eGFR ≥ 30 mL/min per 1.73 m^2 (using the CKD-EPI);
• 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

• Subjects with abnormal laboratory tests, including but not limited to the following:

• White blood cell count < 1.5×109/L
• Neutrophils < 1.0×109/L
• Hemoglobin < 85.0 g/L
• Platelet count < 80.0×109/L
• Total bilirubin >2×ULN
• ALT>3×ULN
• AST>3×ULN
• Alkaline phosphatase>2×ULN
• Creatine kinase>5×ULN
• IgA<10 mg/dL; or IgG≤400mg/dL；
• Patients with secondary IgA nephropathy, including but not limited to: Henoch-Schonlein purpura, ankylosing spondylitis, systemic lupus erythematosus, etc.;
• Patients with other types of glomerular disease such as crescentic glomerulonephritis, minimal change nephropathy with IgA deposition;;
• Renal transplant;
• Patients with cirrhosis, as assessed by the investigator;
• Patients who experienced any of the following cardiovascular and cerebrovascular events within 24 weeks prior to randomization: myocardial infarction, unstable angina, ventricular arrhythmia, NYHA Class II or higher heart failure, stroke, etc.;
• Sitting position SBP>140 mmHg or DBP>90 mmHg for at least once at 2 visits during the screening period;
• Patients with poorly controlled type 1 and type 2 diabetes (glycated hemoglobin A1c[HbA1c] > 8% or 64mmol/mol);
• Treatment with immunosuppressants within 12 weeks prior to randomization, including but not limited to cyclophosphamide, azathioprine, mycophenolate, leflunomide, tacrolimus, cyclosporine, Tripterygium wilfordii;
• Treatment with anti-CD20 therapy (for example, Rituximb Injection) within 24 weeks prior to randomization;
• 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;
• Had hospitalization or intravenous anti-infective therapy for active infection within 4 weeks prior to randomization;
• Patients with active tuberculosis;
• Hepatitis B: patients with active or latent hepatitis B (potive HBcAb and HBV-DNA); According to the test results of hepatitis B five items, subjects with positive HBsAg will be excluded; subjects who are HBsAg-negative but HBcAb-positive, whether HBsAb is positive or negative, should be tested for HBV-DNA: if HBV-DNA is positive, patients should be excluded; if HBV-DNA is negative, patients can participate in the trial, and subjects are advised to take oral entecavir for prophylactic antiviral therapy during the trial;
• Patients with hepatitis C;
• Patients with HIV infection;
• Patients with malignancy within the past 5 years, except for treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, colon polyps, or cervical cancer in situ;
• Pregnant women, lactating women, and subjects with childbearing plans during the trial;
• Allergic to biological products of human origin;
• Participated in any clinical trial within 4 weeks or within 5 times the half-life of the investigational drug participating (whichever is longer) prior to randomization;
• Received live vaccination within 4 weeks prior to randomization;
• Drug or alcohol abuse/dependence within 52 weeks prior to randomization;
• Other circumstances that, in the opinion of the investigator, are not suitable for participation in this study.