BACKGROUND: Complement 3 (C3) glomerulopathy is a rare autoimmune disorder characterized by activation of the alternative complement pathway with isolated or dominant complement 3 deposition in glomeruli. Patients with C3 glomerulopathy may develop progressive deterioration in kidney function and kidney failure. METHODS: We studied the safety and efficacy of avacopan 30 mg twice daily in patients with C3 glomerulopathy (N=57) with elevated (>
244 ng/ml) and normal (≤244 ng/ml) levels of membrane attack complex or terminal complement complex (C5b-9) in a randomized, double-blind, placebo-controlled, phase 2 trial, with kidney biopsies performed prerandomization and at 26 and 52 weeks. The primary outcome was the percent change from baseline to week 26 in C3 Glomerulopathy Histological Index for disease activity. RESULTS: The study was conducted in patients with C3 glomerulopathy, including C3 GN and dense deposit disease. The median study duration was 60.0 weeks (interquartile range, 59.9–61.0). There were no significant differences in the primary outcome between the avacopan and the placebo group—least squares mean treatment difference (95% confidence interval)= −0.0 (−1.9 to 1.8). The secondary measures of efficacy including C3 Glomerulopathy Histological Index for disease chronicity, urine protein:creatinine ratio, and eGFR were not different between treatment groups. The overall incidence and type of adverse events for both treatment groups were comparable. No deaths were reported during the study, and no new safety signals were detected. CONCLUSIONS: The primary end point for the study was not met
other clinical effects of avacopan to improve certain key kidney function parameters and slow disease progression were variable and require further evaluation.