Partnering to treat an Orphan Disease Duchenne Muscular Dystrophy

合作治疗孤儿病杜氏肌营养不良症

• 批准号: 8599246
• 负责人: STANLEY C FROEHNER
• 金额: $ 293.31万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-18 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8599246
• 关键词: Adolescent; Adrenal Cortex Hormones; Adverse effects; Affect; Award; Clinic; Clinical Trials; Country; Development; Disease; Dose; Double-Blind Method; Drug Kinetics; Duchenne muscular dystrophy; Institutes; Investments; Life; Muscular Dystrophies; Myocardium; Nature; Oral; Pediatric Hospitals; Pharmaceutical Preparations; Pharmacodynamics; Pharmacological Treatment; Phase; Phenotype; Placebo Control; Randomized; Rare Diseases; Research Personnel; Safety; Site; Skeletal Muscle; Toxicology; Universities; Washington; boys; efficacy testing; experience; functional improvement; mouse model; novel therapeutics; preclinical study; safety study

Duchenne muscular dystrophy (DMD) is a severely disabling and fatal disorder. It is the most common muscular dystrophy, affecting 1:5000 boys worldwide; however, it is an orphan disease which has received relatively little investment toward the development of novel therapeutics. Consequently, there are no good treatments for this devastating disorder. In this application, Dr. Kathryn Wagner from the Kennedy Krieger Institute and Dr. Stanley Froehner from the University of Washington propose to repurpose a Sanofi compound for Duchenne muscular dystrophy. In the UH2 portion of the award, Dr. Froehner will test efficacy of the compound in the mdx/utr mouse model of DMD and will oversee juvenile toxicology studies performed by a CRO. Following timely IND filing with the FDA, Dr. Wagner and Dr. Jerry Mendell at Nationwide Children's Hospital will conduct Phase Ib SAD and MAD studies for safety and dose finding in a limited number of DMD subjects. In the UH3 portion of the award, Phase IIa studies in DMD boys will be conducted at multiple sites across the country. Investigators at all sites have active DMD clinics and experience in DMD clinical trials. The Phase IIa study will determine if the compound results in functional improvement in DMD as well as whether sustained administration is safe and well tolerated in DMD. Given the life threatening and disabling nature of DMD, the Phase IIa is anticipated to be the pivotal clinical trial for seeking provisional FDA approval.

杜氏肌营养不良症 (DMD) 是一种严重致残且致命的疾病。它是最常见的肌营养不良症，影响全球 1:5000 的男孩；然而，它是一种孤儿疾病，在开发新疗法方面获得的投资相对较少。因此，对于这种破坏性疾病没有好的治疗方法。在本申请中，肯尼迪克里格研究所的 Kathryn Wagner 博士和华盛顿大学的 Stanley Froehner 博士提议重新利用赛诺菲化合物治疗杜氏肌营养不良症。在该奖项的 UH2 部分中，Froehner 博士将测试该化合物在 DMD 的 mdx/utr 小鼠模型中的功效，并将监督 CRO 进行的幼年毒理学研究。在及时向 FDA 提交 IND 申请后，全国儿童医院的 Wagner 博士和 Jerry Mendell 博士将开展 Ib 期 SAD 和 MAD 研究，以在有限数量的 DMD 受试者中进行安全性和剂量研究。在该奖项的 UH3 部分中，DMD 男孩的 IIa 期研究将在全国多个地点进行。所有中心的研究人员都拥有活跃的 DMD 诊所和 DMD 临床试验经验。 IIa 期研究将确定该化合物是否能改善 DMD 的功能，以及持续给药是否安全且耐受性良好。鉴于 DMD 危及生命和致残的性质，IIa 期预计将成为寻求 FDA 临时批准的关键临床试验。