A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Patients With IgA Nephropathy

Background: IgAN is the leading primary glomerulonephritis worldwide. Up to 40% of patients develop kidney failure within ˜20 years of diagnosis. Current treatment consists of optimized supportive care including renin-angiotensin aldosterone system (RAAS) blockade. New therapies targeting the underlying disease pathophysiology are needed. Emerging data suggest that the B cell growth factor, A Proliferation Inducing Ligand (APRIL), plays a key role in the pathogenesis of IgAN and may be an ideal target. Sibeprenlimab (VIS649), a humanized IgG2 monoclonal antibody (mAb) that inhibits APRIL, is being evaluated for the treatment of IgAN. Methods: The VISIONARY Trial (NCT05248646) is a global Phase 3 randomized controlled trial which will assess the efficacy and safety of sibeprenlimab in adult patients with IgAN. Approximately 450 patients with biopsy-confirmed IgAN will be randomized to receive 400mg sibeprenlimab subcutaneously or placebo for 24 months, while continuing to receive standard of care. Key inclusion criteria: on maximally tolerated RAAS blockade, 24 hr uPCR ≥ 0.75 g/g or urine protein ≥ 1.0 g/day, eGFR ≥ 30 mL/min/1.73 m2. Patients with secondary IgAN, coexisting kidney disease, IgG < 600 mg/dL, MEST-C score T2 or C2 will not be included in the study. An exploratory cohort of 20 patients with eGFR 20-30 mL/min/1.73 m2 will also be enrolled. The primary efficacy endpoint is to evaluate the change in 24 hr uPCR at 9 months compared with baseline. Key secondary efficacy endpoint is to evaluate the change in annualized eGFR slope over 24 months. Additional secondary endpoints include clinical remission, safety, pharmacodynamics, and anti-drug Ab. Patients completing the trial will be eligible for a 24-month open label extension study (NCT05248659). Results: Results of study expected later when study is complete. Conclusions: Sibeprenlimab is a mAb that blocks APRIL, a B cell growth factor implicated in the pathogenesis of IgAN. A pivotal phase 3 trial is under way to assess the efficacy and safety of sibeprenlimab for the treatment of IgAN. Funding: Commercial Support - Otsuka Pharmaceuticals Development & Commercialization, Inc.