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

Area of Science:

• Nephrology
• Immunology
• Clinical Trials

Background:

• IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of kidney failure globally.
• There is a critical need for treatments targeting the immune drivers of IgAN to improve long-term patient outcomes.
• Sibeprenlimab is an investigational drug that inhibits APRIL, a key factor in pathogenic galactose-deficient IgA1 (Gd-IgA1) production.

Purpose of the Study:

• To summarize the study design of the phase 3 VISIONARY trial.
• To report the baseline characteristics of patients with IgA nephropathy enrolled in the trial.
• To evaluate the efficacy and safety of subcutaneous sibeprenlimab in a representative IgAN population.

Main Methods:

• The VISIONARY trial is a multicenter, double-blind, placebo-controlled study (NCT05248646).
• Adults with biopsy-confirmed IgA nephropathy were randomized 1:1 to receive sibeprenlimab (400 mg s.c. every 4 weeks) or placebo for 26 doses.
• The primary endpoint is the change in 24-hour urine protein-to-creatinine ratio (uPCR-24 h) at 9 months from baseline.

Main Results:

• The trial enrolled 510 patients across 31 countries, with a median age of 42.0 years.
• The population was diverse, with 58.8% males and 59.0% of Asian ethnicity.
• Baseline characteristics included a mean uPCR-24 h of 1.54 g/g and a mean eGFR of 64.2 ml/min/1.73 m².

Conclusions:

• The VISIONARY trial is the largest IgA nephropathy trial conducted to date.
• It evaluates sibeprenlimab in a broadly representative population at high risk for disease progression.
• This study aims to provide crucial data on the efficacy and safety of sibeprenlimab for IgAN treatment.