Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study

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

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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