A Phase 2 Randomized, Double-Blind, Placebo-Controlled Crossover Trial to Evaluate the Safety and Efficacy of Subcutaneous Injections of Elamipretide in Subjects With Genetically Confirmed Barth Syndrome Followed by Open-Label Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Part 1: Distance Walked During the 6-Minute Walk Test (6MWT) by Visit
研究概览
简要总结
A randomized, double-blind cross over trial to evaluate the safety, efficacy, and tolerability of elamipretide in subjects with Barth syndrome.
详细描述
A phase 2 randomized, double-blind, placebo-controlled crossover trial to evaluate the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in subjects with genetically confirmed Barth syndrome followed by open-label treatment extension. Part 1 was a randomized, double-blind, placebo-controlled, crossover trial to assess safety, tolerability, and efficacy single daily subcutaneous (SC) doses of 40 mg elamipretide administered for 12 weeks in subjects with Barth syndrome. Part 2: This was an open-label extension trial to assess the long-term safety, tolerability, and longitudinal trends in efficacy single daily SC doses of 40 mg elamipretide for up to 192 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed Barth Syndrome
- •Male aged 12 and above
- •At the screening visit, eGFR must meet the following:
- •Body weight >30 kg AND eGFR ≥ 90mL/min at screening
- •Body weight >40kg AND eGFR ≥60 but <90mL/min/ 1.73m² at screening
- •Ambulatory and impaired during the baseline 6MWT
- •On stable medication for 30 days prior to the baseline visit
排除标准
- •Participated in another interventional clinical trial within 30 days of or is currently enrolled in a non-interventional clinical trial at the baseline visit potentially confounding with this trial
- •Prior or current medical condition that would prevent the subject from safely participating in the trial
- •Undergone any inpatient hospitalizations within 30 days of the baseline visit
- •Is undergoing an apparent pubertal growth spurt
- •Has uncontrolled hypertension
- •History of substance abused within the year before the baseline visit or is likely to be uncompliant
- •History of heart transplantation or current placement on the waiting list for a heart transplant
- •For subjects with an ICD: known occurrence of ICD discharge in the 3 months prior to the baseline visit
- •For subjects without an ICD: expected to undergo an implantation of an ICD during the conduct of the study
- •Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or has received prior radiation therapy to the chest
- •Recipient of stem cell or gene therapy or is currently being treated by a therapeutic investigational device
研究组 & 干预措施
Elamipretide, then Placebo
Experimental Part 1: 12 weeks of single daily SC doses of 40 mg elamipretide in Treatment Period 1 followed by 12 weeks of treatment with placebo in Treatment Period 2 (separated by a 4 week washout period).
Experimental Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks
干预措施: Elamipretide (Drug)
Elamipretide, then Placebo
Experimental Part 1: 12 weeks of single daily SC doses of 40 mg elamipretide in Treatment Period 1 followed by 12 weeks of treatment with placebo in Treatment Period 2 (separated by a 4 week washout period).
Experimental Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks
干预措施: Placebo (Drug)
Placebo , then Elamipretide
Placebo Comparator Part 1: 12 weeks of single daily SC doses of placebo in Treatment Period 1 followed by 12 weeks of treatment with 40 mg elamipretide in Treatment Period 2 (separated by a 4 week washout period).
Placebo Comparator Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks
干预措施: Elamipretide (Drug)
Placebo , then Elamipretide
Placebo Comparator Part 1: 12 weeks of single daily SC doses of placebo in Treatment Period 1 followed by 12 weeks of treatment with 40 mg elamipretide in Treatment Period 2 (separated by a 4 week washout period).
Placebo Comparator Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Distance Walked During the 6-Minute Walk Test (6MWT) by Visit
时间窗: Pre-dose to Week 12 (end of treatment)
Average distance walked in meters during the 6-minute walk test (6MWT) at end of treatment, where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period.
Part 1: Total Fatigue Score Based on the BTHS-SA by Visit.
时间窗: Pre-dose, Weeks 1, 4, 8, and 12 (end of treatment)
Total Fatigue Score (Q1, Q2, and Q4) Based on the BarTH Syndrome Symptom Assessment (BTHS-SA) by visit at predose, Weeks 1, 4, 8, and 12 (end of treatment). The BTHS-SA is 3-question fatigue assessment using a 0 to 4-point scale for each question where no fatigue =0 and very severe fatigue =4, with scores from all 3 questions combined and averaged for all subjects; a lower score means better outcome, higher score means a worse outcome. Combined Min score=0, max score =12. Weekly values are based on the weekly average of the last 7 days before the site or visiting nurse visit for both periods. Results from each 12-week period were combined, where end of treatment for Period 1 =Visit 5 (week 12), and End of Period 2 = Visit 10 (week 12)
次要结局
- Part 2: Distance Walked During the 6MWT(Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192)
- Part 1: Muscle Strength as Measured by HHD by Visit(Pre-dose to Week 12 (end of treatment))
- Part 1: Patient Global Impression Scales of Symptoms(Pre-dose, Week 1, Week 12 (end of treatment))
- Part 2: Change From Baseline: Muscle Strength by HHD (Newtons) by Visit(Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192)
- Part 2: Change From Baseline: CGI Symptom Scale(Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192)
- Part 2: Change From Baseline: Total Fatigue Score (Q1, Q2, and Q4) Based on the BTHS-SA by Visit(Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192)
- Part 2: Change From Baseline: 5X Sit to Stand by Visit(Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192)
- Part 1: 5XSST by Visit(Pre-dose to Week 12 (end of treatment))
- Part 1: SWAY Application Balance Assessments by Visit(Pre-dose to Week 12 (end of treatment))
- Part 2: Change From Baseline: SWAY Application Balance Assessment(Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192)
- Part 2: Change From Baseline: Patient Global Impression Scales of Symptoms by Visit(Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192)
- Part 1: Part 1: Clinician Global Impression(Pre-dose to Week 12 (end of treatment))