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: 10436136
• 负责人: Peter Wallace Stacpoole
• 金额: $ 49.64万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436136
• 关键词: Phase; Trial; DCA; PDC; Deficiency; 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 先天丙酮酸脱氢酶复合物（PDC）缺陷（PDCD）是威胁生命的 新陈代谢整合的线粒体疾病，其中碳水化合物燃料有效地转化为 能量受到干扰。 PDCD没有可靠的疗法。但是，二氯乙酸（DCA）代表 通过刺激残留的PDC活性，降低多余的PDC活性，对该疾病的潜在疗法有针对性的治疗 并改善线粒体能量学。这个背景和我们的初步数据表明DCA可能 受益于PDCD儿童的临床状况。我们与FDA紧密合作，并由父母驱动 组织开发适当的研究设计并确定潜在的主题。我们现在建议 进行一项为期4年的3阶段临床试验，以测试口服DCA的假设 与安慰剂相比，受影响儿童的功能将宽容且可用于长期使用。 我们的主要终点将基于改善的临床状况，由小说观察者确定 报告的结果（obsro）度量。我们的次要终点将包括1）确认更好 Karnofsky/Lansky绩效量表的临床结果在患有生活的儿童中 威胁性疾病； 2）乳酸血症降低。