A Phase 2 Randomized, Double-Blind, Placebo-Controlled Crossover Study to Evaluate Safety, Tolerability, and Efficacy of Subcutaneous Injections of MTP-131 in Subjects With Mitochondrial Myopathy Previously Treated in the SPIMM-201 Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Distance Walked on the 6-minute Walk Test (6MWT) by Visit
研究概览
简要总结
This randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (PMM) to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of subcutaneous elamipretide in this patient population.
详细描述
This randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (PMM) who had completed participation in the SPIMM-201 study where they had received 5 days of intravenous (IV) elamipretide (0.01, 0.10, or 0.25 mg/kg/hour infused for 2 hours) or placebo (randomized 3:1). The primary objective was to evaluate the effect of single daily subcutaneous (SC) doses of elamipretide administered for 4 weeks on the 6-minute walking distance (6MWD).
Subjects were randomized (1:1) to one of two sequence groups: 4-weeks of treatment with 40 mg elamipretide administered once daily SC in Treatment Period 1 followed by 4-weeks of treatment with placebo administered once daily SC in Treatment Period 2 (separated by a 4-week washout period), or vice versa. Each sequence group went through 5 distinct periods: Screening, Treatment Period 1, Washout, Treatment Period 2, and Follow-Up. Safety, tolerability, pharmacokinetics (PK), and efficacy of subcutaneous elamipretide in this patient population were analyzed.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject completed participation in the SPIMM-201 study without a significant protocol deviation that would suggest the subject may not be able to complete all study requirements in the opinion of the Sponsor
- •Subject must reside in North America for the duration of the study
- •Subject has not received study drug in the SPIMM-201 study within 3 weeks prior to Screening
- •Women of childbearing potential must agree to use 1 of the methods of birth control specified in the protocol from the date they sign the informed consent form (ICF) until two months after the last dose of study drug
- •Subject has been on stable (unchanged and constant) medications (including over-the counter treatments, vitamins, or supplements) for at least 1 month prior to the Baseline Visit
排除标准
- •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 study requirements (i.e. unstable angina or recent myocardial infarction)
- •Subject has received any investigational compound and/or has participated in another interventional clinical study within 30 days prior to the Baseline Visit or is concurrently enrolled in any non-interventional research of any type judged to be scientifically or medically incompatible with the study as deemed by the Investigator in consultation with the Sponsor
- •Subject experienced an adverse reaction to study drug in the SPIMM-201 study that contraindicates further treatment with elamipretide in the opinion of the Investigator and/or Sponsor
- •Female subjects who are pregnant, planning to become pregnant, or lactating
- •Subject has undergone an in-patient hospitalization within the 1 month prior to the Screening Visit or is likely to need in-patient hospitalization or a surgical procedure during the course of the study
- •Subject has a creatinine clearance ≤30 mL/min as calculated by the Cockcroft Gault equation
- •Subject has a corrected QT interval (QTc) elongation defined as a QTc >450 msec in male subjects and >480msec in female subjects. Note: At the initial electrocardiogram (ECG), if QTc exceeds these parameters, the ECG may be repeated 2 more times, and the average of the 3 QTc values used to determine the subjects eligibility
- •Subject has uncontrolled hypertension in the judgment of the Investigator (e.g. elevated above >160 mmHg systolic or >100 mmHg diastolic despite appropriate treatment on two consecutive readings)
- •Subject has a history of clinically significant hypersensitivity or allergy to any of the excipients contained in the study drug
- •Subject has a history of active alcoholism or drug addiction during the year before the Screening Visit
研究组 & 干预措施
Elamipretide, Then Placebo
Participants first received 40 mg of elamipretide once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received placebo administered once daily subcutaneously for 4 weeks.
干预措施: Placebo (Drug)
Elamipretide, Then Placebo
Participants first received 40 mg of elamipretide once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received placebo administered once daily subcutaneously for 4 weeks.
干预措施: Elamipretide (Drug)
Placebo, Then Elamipretide
Participants first received placebo once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received 40 mg of elamipretide once daily subcutaneously for 4 weeks.
干预措施: Elamipretide (Drug)
Placebo, Then Elamipretide
Participants first received placebo once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received 40 mg of elamipretide once daily subcutaneously for 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Distance Walked on the 6-minute Walk Test (6MWT) by Visit
时间窗: End of Week 4 and End of Week 12
Distance in meters walked on the 6-minute walk test (6MWT) at end of treatment, where end of treatment means end of week 4 for Period 1 and end of week 12 for Period 2.
次要结局
- Average Hip Accelerator Counts by Day(Last 7 days prior to the date of end of treatment visit)
- Neuro-QoL Fatigue Short Form Score: Total T-Scores (Question 1-8)(End of Week 4 and End of Week 12)
- Physician Global Assessment (PhGA) By Visit, Categorical(End of Week 4 and End of Week 12)
- Wrist Accelerometer Counts by Day(Last 7 days prior to the date of end of treatment visit)
- Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score by Week(Last 7 days of Week 4 and Last 7 days of Week 12)
- Triple Timed Up and Go (3TUG) Test by Visit(End of Week 4 and End of Week 12)
- Patient Global Assessment [PGA] Score by Visit, Continuous(End of Week 4 and End of Week 12)
- Patient Global Assessment by Visit, Categorical(End of Week 4 and End of Week 12)
- Physician Global Assessment (PhGA) By Visit, Continuous(End of Week 4 and End of Week 12)