A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of High Doses of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 59
- 主要终点
- Part 1: Incidence of Adverse Events (AEs)
研究概览
简要总结
Part 1 (dose escalation) will evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10 participants with DMD; Part 2 (dose finding and dose comparison) will evaluate the efficacy and safety of the high doses (100 mg/kg and 200 mg/kg) of eteplirsen compared with that of the 30 mg/kg dose of eteplirsen, in approximately 144 participants with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 is open-label, dose escalation; Part 2 is double-blind, dose finding, and dose comparison
入排标准
- 年龄范围
- 4 Years 至 13 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.
- •Ambulatory participant, able to perform TTRISE in 10 seconds or less at the time of screening visit.
- •Able to walk independently without assistive devices.
- •Have intact right and left biceps muscles or an alternative upper arm muscle group.
- •Have been on a stable dose or dose equivalent of oral corticosteroids for at least 12 weeks prior to randomization and the dose is expected to remain constant (except for modifications to accommodate changes in weight and stress-related needs as per the recently published guidelines throughout the study.
- •For ages 7 years and older, has stable pulmonary function (forced vital capacity ≥50 percent (%) of predicted and no requirement for nocturnal ventilation). For ages 4 to 6 years, does not require support from ventilator or non-invasive ventilation at time of screening.
排除标准
- •Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
- •Current or previous treatment with any other experimental pharmacologic treatment for DMD or any prior exposure to antisense oligonucleotide, gene therapy or gene editing; except the following: Ezutromid in the last 12 weeks prior to first dose; Drisapersen in the last 36 weeks prior to first dose; Suvodirsen in the last 12 weeks prior to first dose; Vamorolone in the last 12 weeks prior to first dose; Eteplirsen (previous or current use); and Tamoxifen in the last 4 weeks prior to first dose.
- •Major surgery within 3 months prior to randomization.
- •Presence of any other significant neuromuscular or genetic disease other than DMD.
- •Presence of any known impairment of renal function and/or other clinically significant illness.
- •Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than <50% on the screening echocardiogram or Fridericia's correction formula (QTcF) ≥450 millisecond based on the screening electrocardiograms (ECGs).
- •Other inclusion/exclusion criteria apply.
研究组 & 干预措施
Part 1: Eteplirsen
Participants will receive eteplirsen 100 mg/kg once weekly for at least 4 weeks, followed by eteplirsen 200 mg/kg once weekly for at least 4 weeks.
干预措施: Eteplirsen (Drug)
Part 2: Eteplirsen 30 mg/kg
Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.
干预措施: Eteplirsen (Drug)
Part 2: Eteplirsen 100 mg/kg
Randomized participants will receive eteplirsen 100 mg/kg once weekly for up to 144 weeks.
干预措施: Eteplirsen (Drug)
Part 2: Eteplirsen 200 mg/kg
Randomized participants will receive eteplirsen 200 mg/kg once weekly for up to 144 weeks.
干预措施: Eteplirsen (Drug)
结局指标
主要结局
Part 1: Incidence of Adverse Events (AEs)
时间窗: Up to Week 148
Part 2: Change From Baseline at Week 144 in the NSAA Total Score (for Final Analysis)
时间窗: Baseline, Week 144
Part 2: Change from Baseline at Week 72 or Week 96 in NSAA Total Score (for Conditional Efficacy Interim Analysis)
时间窗: Baseline, Week 72 or Week 96
次要结局
- Part 2: Change From Baseline in Time to Rise From the Floor, Time to Complete 10-Meter Walk/Run, and the Timed Stair Ascend Test(Baseline, Week 144)
- Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT)(Baseline, Week 144)
- Part 2: Change from Baseline at Week 144 in Forced Vital Capacity Percent Predicted (FVC%p)(Baseline, Week 144)
- Part 2: Time to Loss of Ambulation (LOA)(Baseline up to Week 144)
- Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression(Baseline, Postdose (at Week 24, Week 48, or Week 144))
- Part 2: Incidence of Adverse Events (AEs)(Baseline up to Week 148)
- Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen(0 (predose) to 2 hours postdose up to Week 144)