BACKGROUND Complement 3 (C3) glomerulopathy is a rare autoimmune disorder characterized by activation of the alternative complement pathway with isolated or dominant C3 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 C5b-9 in a randomized, double-blind, placebo-controlled, phase 2 trial, with kidney biopsies performed pre-randomization and at 26 and 52 weeks. The primary outcome was the percent change from baseline to week 26 in C3 glomerulopathy histologic index for disease activity. RESULTS The study was conducted in patients with C3 glomerulopathy, including C3 glomerulonephritis and DDD. The median study duration was 60.0 weeks (interquartile range 59.9 to 61.0). There were no significant differences in the primary outcome between the avacopan and the placebo group; least square mean treatment difference (95% CI) = -0.0 (-1.9 to 1.8). The secondary measures of efficacy including C3 Glomerulopathy Histological Index for disease chronicity, urine protein:creatinine ratio (UPCR), and estimated glomerular filtration rate (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.

中文翻译：

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Avacopan 在 C3 肾小球病患者中的安全性和有效性：随机、双盲临床试验。


背景 补体 3 （C3） 肾小球病是一种罕见的自身免疫性疾病，其特征是替代补体途径激活，伴有孤立或显性 C3 沉积在肾小球中。C3 肾小球病患者可能会出现肾功能进行性恶化和肾衰竭。方法 我们在一项随机、双盲、安慰剂对照的 2 期试验中研究了 avacopan 30 mg 每日两次对 C5b-9 水平升高 （> 244 ng/mL） 和正常 （≤ 244 ng/mL） 的 C3 肾小球病 （N=57） 患者的安全性和有效性，肾活检在随机化前以及 26 和 52 周进行。主要结局是 C3 肾小球病疾病活动组织学指数从基线到第 26 周的百分比变化。结果 该研究是在 C3 肾小球病患者中进行的，包括 C3 肾小球肾炎和 DDD。中位研究持续时间为 60.0 周 （四分位距 59.9 至 61.0）。avacopan 组和安慰剂组之间的主要结局没有显著差异;最小二乘平均治疗差异 （95% CI） = -0.0 （-1.9 至 1.8）。疗效的次要指标包括 C3 肾小球病慢性组织学指数、尿蛋白：肌酐比值 （UPCR） 和估计肾小球滤过率 （eGFR） 在治疗组之间没有差异。两个治疗组的总体发生率和不良事件类型具有可比性。研究期间未报告死亡病例，也未检测到新的安全性信号。结论 未达到该研究的主要终点;avacopan 改善某些关键肾功能参数和减缓疾病进展的其他临床效果是可变的，需要进一步评估。