a study of telitacicept in patients with primary immunoglobulin a（iga） nephropathy

Conditions: Primary IgA Nephropathy

Summary: 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.

Keywords: autoimmune diseases immune system diseases iga nephropathy