Interim Analysis of APPLAUSE-IgAN Iptacopan Study

APPLAUSE-IgAN is a phase 3 study to determine the efficacy and safety of iptacopan versus placebo in patients with IgA nephropathy (IgAN). Dana V. Rizk and fellow researchers presented prespecified interim analysis (IA) results of the study during the National Kidney Foundation Spring Clinical Meetings.

The randomized, double-blind, placebo-controlled study evaluates iptacopan plus optimized supportive care in patients with biopsy-confirmed IgAN and proteinuria ≥1 g/g by urine protein-to-creatinine ratio (UPCR) from 24-hour urine collection (UPCR-24h) despite maximally tolerated renin-angiotensin system inhibitors for ≥3 months. The researchers randomized patients 1:1 to receive iptacopan 200 mg or placebo twice daily for 24 months.

At the prespecified IA, researchers evaluated 125 patients for iptacopan and 125 patients for placebo. The safety analyses included 222 patients for iptacopan and 221 for placebo. The baseline characteristics were balanced across treatment arms.

Iptacopan proved superior to placebo in reducing proteinuria (UPCR-24h) from baseline at month 9 (M9), with a reduction of 38.3% (95% CI, 26.0%-48.6%; one-sided P<.0001) versus placebo. UPCR from first morning void declined as early as week 2; the reduction from baseline at M9 with iptacopan versus placebo was 35.8% (95% CI, 22.6%-46.7%).

About twice as many patients on iptacopan reached UPCR-24h <1 g/g at M9 compared with the placebo group (marginal proportion, 42.5% [95% CI, 34.5%-50.5%] vs 21.9% [95% CI, 14.8%-29.0%], respectively). Adverse events prevented 2.7% of patients in each group from completing treatment. Otherwise, iptacopan was well tolerated with an infection rate not exceeding that of the placebo group.

The authors concluded that “APPLAUSE-IgAN demonstrated superiority of iptacopan versus placebo in proteinuria reduction at M9, with early onset and consistency of effect. Iptacopan was well tolerated with a favorable safety profile.”

Source: Rizk DV, Kollins D, Papachristofi O, et al. Efficacy and safety of iptacopan in patients with IgA nephropathy (IgAN): interim analysis (IA) of the phase 3 APPLAUSE-IgAN study. Presented at the National Kidney Foundation Spring Clinical Meetings 2024; May 14-18, 2024; Long Beach, California.