Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD.
Polycystic Kidney Disease Foundation, Kansas City, MO.
Am J Kidney Dis. 2019 Apr;73(4):533-541. doi: 10.1053/j.ajkd.2018.11.001. Epub 2018 Dec 29.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Expansion of multiple cysts throughout both kidneys is thought to lead to progressive loss of kidney function and kidney failure in some patients. In recent years, much has been learned about the pathophysiology of ADPKD. However, to date, only one therapy has been approved in the United States and in other regions for the treatment of ADPKD. Feasible end points and a clear regulatory pathway may stimulate further development in this area and ultimately lead to more treatments for ADPKD successfully reaching the market. In July 2016, the PKD Outcomes Consortium under the auspices of the Critical Path Institute and the PKD Foundation convened a PKD Summit to facilitate a discussion among patients, regulators, pharmaceutical sponsors, and academic clinical trialists regarding trial end points and the regulatory path to approval of new drugs for ADPKD. Following the summit, participants continued the dialogue using regularly scheduled teleconferences. This article addresses key considerations related to the design of clinical trials in ADPKD based on these discussions.
常染色体显性多囊肾病(ADPKD)是最常见的遗传性肾病。人们认为,双肾内多个囊肿的扩张会导致一些患者的肾功能逐渐丧失和肾衰竭。近年来,人们对 ADPKD 的病理生理学有了更多的了解。然而,迄今为止,美国和其他地区仅批准了一种用于治疗 ADPKD 的疗法。可行的终点和明确的监管途径可能会刺激该领域的进一步发展,并最终为 ADPKD 带来更多成功进入市场的治疗方法。2016 年 7 月,在关键路径研究所和 PKD 基金会的主持下,PKD 结果联合会召集了一次 PKD 峰会,以促进患者、监管机构、制药赞助商和学术临床试验人员之间就试验终点和批准治疗 ADPKD 的新药的监管途径进行讨论。峰会结束后,参与者继续通过定期电话会议进行对话。本文基于这些讨论,介绍了与 ADPKD 临床试验设计相关的关键考虑因素。