METHODS: We randomly assigned adults with IgA nephropathy to receive subcutaneous sibeprenlimab (at a dose of 400 mg) or placebo every 4 weeks. The key secondary end point was the annualized slope of the eGFR over 24 months. Other secondary end points included the change in eGFR from baseline to 24 months, a composite kidney end point of kidney-function decline or kidney failure, and pharmacodynamic and safety end points.

RESULTS: A total of 510 patients underwent randomization - 259 to receive sibeprenlimab and 251 to receive placebo. The annualized eGFR slope over 24 months was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], -0.4 to 0.9) with sibeprenlimab and -4.2 ml per minute per 1.73 m2 per year (95% CI, -4.9 to -3.6) with placebo (between-group difference, 4.5 ml per minute per 1.73 m2 per year; 95% CI, 3.6 to 5.4; P<0.001). The least-squares mean treatment difference for the change in eGFR from baseline to 24 months was 9.2 ml per minute per 1.73 m2 (95% CI, 7.1 to 11.4; P<0.001). A composite kidney end-point event occurred in 1 patient (0.4%) in the sibeprenlimab group and in 28 patients (11.2%) in the placebo group (adjusted difference, -10.8 percentage points; hazard ratio, 0.029; 95% CI, 0.004 to 0.214; P<0.001). Adverse events occurred in 235 patients (90.7%) in the sibeprenlimab group and 226 patients (90.0%) in the placebo group; serious adverse events occurred in 21 patients (8.1%) and 32 patients (12.7%), respectively; and serious infections in 5 patients (1.9%) and 10 patients (4.0%). No deaths were reported.