A Phase 3 Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Treatment Extension
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 218
- 试验地点
- 50
- 主要终点
- Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
研究概览
简要总结
This is a multicenter phase 3 randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the safety and efficacy of daily subcutaneous injections of elamipretide in subjects with primary mitochondrial myopathy. This will be followed by an open-label treatment extension.
详细描述
Part 11 is a 24-week, randomized, double-blind, parallel-group, placebo-controlled assessment of the efficacy and safety of single daily subcutaneous (SC) doses of 40 mg elamipretide (vs placebo) administered with the elamipretide delivery system as a treatment for subjects with primary mitochondrial myopathy (PMM). Part 2 was to assess the long-term safety and tolerability of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for up to 144 weeks.
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)
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide a signed informed consent form prior to participation in any trial-related procedures
- •Agrees to adhere to the trial requirements for the length of the trial, including the use of the elamipretide delivery system
- •Subject is ≥ 16 and ≤ 80 years of age
- •Diagnosed with PMM in the opinion of the investigator and confirmed by an Adjudication Committee
- •Woman of childbearing potential must agree to use a highly effective method of birth control
排除标准
- •Subject has myopathic signs and or/symptoms due to a neuropathic process or gait problem that would interfere with the 6 minute walk test (6MWT), in the opinion of the Investigator
- •Female who are pregnant, planning to become pregnant, or breastfeeding/lactating
- •At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
- •Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial.
- •Subject has clinically significant cardiac disease or prior interventional procedure and/or respiratory disease (medical history or current clinical findings) within 3 months of the Baseline Visit, in the opinion of the Investigator.
- •Subject has QTc elongation (using the correction factor utilized at the clinical site) defined as a QTc >450 msec in male subjects and >480 msec in female subjects.
- •ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following:
- •First degree Atrioventricular bock (AV-block)
- •Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
- •Right bundle branch block
- •Subject has severe vision impairment that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements
- •Subject has a seizure disorder that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements.
- •Active malignancy or any other cancer from which the subject has been disease-free for < 2 years.
- •Subject has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression, in the opinion of the Investigator.
- •Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
- •Subject has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000 cells x10^6/L at the Screening Visit.
- •Subject is currently participating or has participated in an interventional clinical trial (i.e.,investigational product or device, stem cell therapy, gene therapy) within 30 days of the Baseline Visit; or is currently enrolled in a non-interventional clinical trial (except for SPIMM-300) at the Baseline Visit which, in the opinion of the Investigator, may be potentially confounding with results of the current trial (e.g., exercise therapy trial).
- •Subject has previously received elamipretide (MTP-131), for any reason.
- •Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator.
- •Subject has any prior or current medical condition that, in the judgment of the Investigator, would prevent the subject from safely participating in and/or completing all trial requirements.
- •Continuation Criteria:
- •Subjects must continue to be able and willing to adhere to the trial requirements.
- •Subject is appropriate to continue in Part 2 (i.e. subject was compliant in Part 1), in the opinion of the Investigator.
- •Subject has not had a serious adverse event (SAE)/serious adverse device effect (SADE) attributed to the elamipretide delivery system.
- •Subject has not permanently discontinued the elamipretide delivery system.
结局指标
主要结局
Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
时间窗: Baseline to 24 weeks
Change from Baseline in Total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) by visit. Each individual item score ranges from 1 (none) to 4 (severe). The total fatigue score ranges from 4-16. Lower values represent a better outcome. The total fatigue score is the sum of question 1 through question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.
Six-minute Walk Test (6MWT)
时间窗: Baseline to 24 weeks
Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
次要结局
- Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment(Baseline to 24 weeks)
- Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).(Baseline to 24 weeks)
- Neuro-QoL Fatigue Activities of Daily Living(Baseline to 24 weeks)
- Neuro-QoL Fatigue Short Form Score(24 Weeks)