Phase 1 Clinical Trial of rAAV2.5-CMV-mini-Dystrophin Gene Vector in Duchenne Muscular Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
研究概览
简要总结
The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).
详细描述
This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 15 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Known null mutation of the Dystrophin gene
- •Male age of 5 years or older
- •If taking corticosteroids, must have dose unchanged for the past 3 months
- •Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
- •Progressive, symmetrical proximal muscle weakness of arms and legs
排除标准
- •Unable to cooperate for muscle strength testing
- •Joint contractures that prohibit muscle strength testing
- •Concomitant illness
- •Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
- •Controlled substance abuse
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
时间窗: followed for 2 years post injection
Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)
次要结局
- mini-dystrophin gene expression at the site of gene transfer(90 days post injection)
- Maximal Volume Isometric Contraction Testing as a measure of muscle strength(out to 2 years post injection)
研究者
Jerry R. Mendell
Director Center for Gene Therapy
Nationwide Children's Hospital