Phase 3 Trial of DCA in PDC Deficiency IND 028,625 (02/04/2015)

DCA 治疗 PDC 缺陷的 3 期试验 IND 028,625 (02/04/2015)

• 批准号: 9625517
• 负责人: Peter Wallace Stacpoole
• 金额: $ 49.24万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9625517
• 关键词: Phase; Trial; DCA; PDC; Deficiency

Abstract Congenital pyruvate dehydrogenase complex (PDC) deficiency (PDCD) is a life-threatening mitochondrial disease of metabolic integration in which the efficient conversion of carbohydrate fuel into energy is perturbed. There are no proven therapies for PDCD. However, dichloroacetate (DCA) represents targeted potential therapy for this disease by stimulating residual PDC activity, decreasing hyperlactatemia and improving mitochondrial energetics. This background and our preliminary data suggest that DCA may benefit the clinical status of PDCD children. We have worked closely with the FDA and a parent-driven organization to develop an appropriate study design and identify prospective subjects. We now propose to undertake a 4 year phase 3 clinical trial to test the hypotheses that oral DCA will improve at-home functionality of affected children compared to placebo and will be well-tolerated and safe for chronic use. Our primary endpoint will be based on an improved clinical status, as determined by a novel, Observer Reported Outcome (ObsRO) measure. Our secondary endpoints will include 1) confirmation of better clinical outcome by the Karnofsky/Lansky performance scale of home functionality in children with life- threatening disease; and 2) decreased lactatemia.

抽象的 先天性丙酮酸脱氢酶复合物（PDC）缺乏症（PDCD）是一种危及生命的疾病 代谢整合的线粒体疾病，其中碳水化合物燃料有效转化为 能量受到扰乱。 PDCD 尚无行之有效的治疗方法。然而，二氯乙酸盐（DCA）代表 通过刺激残留的 PDC 活性、减少高乳酸血症来治疗这种疾病 并改善线粒体能量。这一背景和我们的初步数据表明 DCA 可能 有利于PDCD儿童的临床状态。我们与 FDA 和家长驱动的机构密切合作 组织制定适当的研究设计并确定未来的受试者。我们现在建议 进行为期 4 年的 3 期临床试验，以测试口服 DCA 将改善家庭治疗的假设 与安慰剂相比，受影响儿童的功能得到改善，并且长期使用具有良好的耐受性和安全性。 我们的主要终点将基于临床状态的改善，由新颖的观察者确定 报告结果 (ObsRO) 衡量标准。我们的次要终点将包括 1) 确认更好 根据卡诺夫斯基/兰斯基儿童家庭功能表现量表得出的临床结果 威胁疾病； 2）降低乳酸血症。