Evaluating Sibeprenlimab in IgA Nephropathy - Rationale and Baseline Data from the VISIONARY Trial.

Introduction: IgA nephropathy is the most common primary glomerulonephritis and a leading cause of kidney failure worldwide. Treatments that target the underlying immune drivers of the disease to improve long-term patient outcomes are needed. Sibeprenlimab, a selective A Proliferation-Inducing Ligand (APRIL) inhibitor that significantly decreases pathogenic galactose-deficient IgA1 (Gd-IgA1) production and immune complex formation, is being investigated in the ongoing phase 3 VISIONARY trial. Here, we summarize the overall study design and report on the baseline characteristics of patients enrolled in the trial. Methods: VISIONARY is a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier, NCT05248646; study date of registration: 2022-02-18). Adults with biopsy-confirmed IgA nephropathy were randomized 1:1 to receive subcutaneous (s.c.) sibeprenlimab 400 mg or placebo once every 4 weeks for 26 doses. The primary end point is the 24-hour urine protein-to-creatinine ratio (uPCR-24 h) at 9 months compared with the baseline. Results: Of 510 enrolled patients across 31 countries, 58.8% were male, 59.0% were Asian, and 57.3% lived in East or South/Southeast Asia. The median age was 42.0 (range, 18.0-83.0) years; 97.8% of patients were using renin-angiotensin system inhibitors (RASis), and 45.1% were using sodium-glucose cotransporter 2 inhibitors. The mean (SD) baseline uPCR-24 h was 1.54 (0.92) g/g. The mean (SD) baseline urine protein was 2.1 (1.3) g/d, and the mean (SD) baseline estimated glomerular filtration rate (eGFR) was 64.2 (25.3) ml/min per 1.73 m2. Conclusion: VISIONARY, the largest IgA nephropathy trial to date, is evaluating the efficacy and safety of s.c. sibeprenlimab in a broadly representative population with IgA nephropathy at high risk of disease progression.