An Open-Label, Multi-Center, Study With a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 37
- 主要终点
- Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at Week 96
研究概览
简要总结
The main objective of this study is to provide evidence of efficacy of eteplirsen (AVI-4658) in Duchenne muscular dystrophy (DMD) patients that are amenable to skipping exon 51. Additional objectives include evaluation of safety, biomarkers and the long-term effects of eteplirsen up to 96 weeks, followed by a safety extension (not to exceed 48 weeks).
详细描述
This is an open-label, multi-center study to evaluate the efficacy and safety of eteplirsen in patients with genotypically confirmed Duchenne muscular dystrophy (DMD) with genetic deletions amenable to exon 51 skipping (treated group), with a concurrent control arm of DMD patients not amenable to exon 51 skipping (untreated group). Following primary efficacy endpoints, dosing will continue to week 144 to evaluate the long term effects of eteplirsen.
Patients in the treated group will receive once weekly intravenous (IV) infusions of 30 mg/kg Eteplirsen for 96 weeks, followed by a safety extension (not to exceed 48 weeks). Patients in the untreated group will not receive treatment.
Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six minute walk test. Patients in the treated group will undergo a muscle biopsy at Baseline and a second muscle biopsy over the course of the study. Patients in the untreated group will not undergo muscle biopsy.
Safety, including adverse event monitoring and routine laboratory assessments, will be continuously monitored for all patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 16 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male 7-16 years old
- •Diagnosed with DMD, genotypically confirmed
- •Stable dose of corticosteroids for at least 24 weeks
- •Have intact right and left alternative upper muscle groups
- •Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters)
- •Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and LVEF of greater than 50%
排除标准
- •Previous treatment with drisapersen or any other RNA antisense agent or any gene therapy within the last 6 months
- •Participation in any other DMD interventional clinical study within 12 weeks
- •Major surgery within 3 months
- •Presence of other clinically significant illness
- •Major change in the physical therapy regime within 3 months
- •Other inclusion/exclusion criteria apply.
研究组 & 干预措施
Treated Group
Approximately 80 patients with genotypically confirmed Duchenne muscular dystrophy (DMD) with genetic deletions amenable to treatment by exon 51 skipping will receive 30 mg/kg of eteplirsen weekly for 96 weeks, followed by a safety extension (not to exceed 48 weeks).
干预措施: eteplirsen (Drug)
结局指标
主要结局
Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at Week 96
时间窗: Baseline, Week 96
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 96 was reported.
次要结局
- Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 96(Baseline, Week 96)
- Number of Participants Having Ability to Rise Independently From the Floor Determined Based on North Star Ambulatory Assessment (NSAA) at Week 96(Week 96)
- Number of Participants Who Lost Ambulation (LOA) by Week 96(Up to Week 96)
- Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Weeks 96(Baseline, Week 96)
- Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Scores at Week 96(Baseline, Week 96)
- Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 96(Baseline, Week 96)