Phase 2 Study of Avacopan for Treatment of C3G, IND 132321, Orphan Designation 16-5590

Avacopan 治疗 C3G 的 2 期研究，IND 132321，孤儿药指定 16-5590

• 批准号: 10015262
• 负责人: Peter M Staehr
• 金额: $ 50万
• 依托单位: CHEMOCENTRYX, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015262
• 关键词: Phase; Study; Avacopan; Treatment; C3G

Project Summary Complement 3 Glomerulopathy (C3G) is an orphan disease which includes C3 glomerulonephritis (C3GN) and the closely related dense deposit disease (DDD), forms of glomerulonephritis. This disease results from abnormal regulation of the alternative complement pathway resulting in unrestrained complement activation. The clinical presentation varies from mild proteinuria to rapid renal deterioration and about half of the individuals with C3G move the End Stage Renal Disease within in 10 years of diagnosis. There are no approved drugs for C3G currently The current treatment recommendations include control of hypertension with angiotensin-converting enzyme (ACE)/angiotensin receptor blocker (ARBs) to empirical use of plasma exchange or infusion. None of these treatments address the dysregulation of the complement system. Hence, there is a significant unmet medical need for novel drugs to treat C3G. Avacopan is an orally active drug that specific inhibitor of the C5a receptor (part of the complement system) and has been shown to be safe and efficacious in Phase 1 and Phase 2 human clinical trials in AAV, and is currently being tested in a Phase 3 AAV trial. More importantly, compelling clinical, laboratory, and kidney biopsy responses have been observed in C3G patients treated with avacopan under a compassionate use protocol. Taken together, these findings provide a strong justification for a human clinical trial to test the safety and efficacy of avacopan as a novel treatment of C3G. This study will enroll 44 patients with C3G at 40 clinical sites in 11 countries. The primary goal of the study is to evaluate the efficacy of avacopan compared to placebo based on histologic changes in kidney biopsies taken before and during treatment. Secondary goals of this study include the evaluation of: 1 The safety of avacopan compared to placebo based on the incidence of adverse events, changes in clinical laboratory measurements, and vital signs; 2 Changes in laboratory parameters of renal disease including estimated glomerular filtration rate (eGFR), proteinuria, and urinary excretion of monocyte chemoattractant protein-1 (MCP- 1) with avacopan compared to placebo; 3 Health-related quality-of-life changes based on Short Form-36 version 2 (SF-36 v2) and EuroQOL-5D-5L (EQ-5D-5L) with avacopan compared to placebo; 4 The pharmacokinetic profile of avacopan in patients with C3G. Additionally, exploratory evaluations studying changes from baseline in markers of alternative complement pathway involvement and other markers of inflammation may be assessed in plasma/serum or urine over the course of the treatment period.

项目摘要 补体3肾小球病（C3G）是一种孤儿疾病，包括C3肾小球肾炎 （C3GN）和密切相关的致密沉积疾病（DDD），肾小球肾炎的形式。这种疾病 替代补体途径异常调节的结果，导致不受约束 补体激活。临床表现从轻度蛋白尿到快速肾脏恶化 大约一半的C3G个体在10年之内移动终阶段肾脏疾病 诊断。目前尚无批准的C3G药物 包括用血管紧张素转换酶（ACE）/血管紧张素受体阻滞剂控制高血压 （ARB）进行血浆交换或输注的经验使用。这些治疗都没有解决 补体系统的失调。因此，对新颖的医学需求很大 治疗C3G的药物。 Avacopan是一种口服活性药物，该药物是C5A受体的特异性抑制剂（补体的一部分 系统），并已显示在第1阶段和第2阶段的人类临床试验中是安全有效的 AAV，目前正在3阶段AAV试验中进行测试。更重要的是，引人注目的临床， 在接受Avacopan治疗的C3G患者中观察到实验室和肾脏活检反应 富有同情心的使用协议。综上所述，这些发现为人类提供了强有力的理由 临床试验，以测试Avacopan作为C3G的新方法的安全性和功效。这项研究会 在11个国家 /地区的40个临床部位招募44例C3G患者。该研究的主要目标是 根据肾脏活检的组织学变化，与安慰剂相比，评估avacopan的功效 在治疗之前和期间服用。这项研究的次要目标包括评估： 1基于不良事件的发生率与安慰剂相比，avacopan的安全性， 临床实验室测量和生命体征的变化； 2肾脏疾病实验室参数的变化，包括估计的肾小球过滤 速率（EGFR），蛋白尿和单核细胞趋化剂蛋白1（MCP-）的尿液排泄 1）与安慰剂相比，avacopan; 3个与健康相关的生活质量变化，基于短形式2版2（SF-36 V2）和 与安慰剂相比，带有Avacopan的EuroQol-5D-5L（EQ-5D-5L）； 4 C3G患者的Avacopan的药代动力学特征。 此外，探索性评估研究了替代标记中基线的变化 可以在血浆/血清中评估补体途径参与和其他炎症标记 或在整个治疗期间的尿液。