Conditions: Mitochondrial Myopathy
Keywords: Mitochondrial Myopathy Primary Mitochondrial Disease Bendavia™ elamipretide
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: no

Brief summary:
Phase 1/2, multi-center, randomized, double-blind, multiple ascending dose, placebo-controlled study that enrolled 36 subjects with mitochondrial myopathy associated with genetically confirmed mitochondrial disease to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MTP-131 in this patient population.

Detailed description:
This multi-center, randomized, double-blind, placebo-controlled study enrolled 36 subjects into 3 cohorts of 12 subjects each to evaluate treatment with 3 ascending doses of intravenous elamipretide (0.01, 0.10, and 0.25 mg/kg/hr infused for 2 hours). After each cohort, a Safety Monitoring Board (SMB) determined if dose escalation to the next higher dose of elamipretide was warranted. Each cohort went through 3 distinct periods: Screening, Treatment, and Follow-up.

The Screening Period started with informed consent and may have lasted up to 40 days. During this period, screening procedures to determine subject eligibility for the study occurred, including confirmation of disease, which incorporated a committee review of the investigator-submitted diagnosis and genetic results. The Treatment Period began on Day 1 (Visit 2) and lasted for 5 days (until Day 5 \[Visit 6\]). Within each cohort, 9 subjects were randomized to active drug and 3 subjects were randomized to placebo on Day 1 and subjects received treatment once a day for 5 consecutive days. Safety, tolerability, and efficacy measures were performed at pre-specified times. The Follow-up Period began at the time of discharge on Day 5. Subjects returned to the study center for the Follow-up Visit on Day 7 (+1 day).

Arms:
arm 1: elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days arm 2: elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days arm 3: elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days arm 4: In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.

Interventions: intervention 1: elamipretide (low dose) intervention 2: elamipretide (intermediate dose) intervention 3: elamipretide (high dose) intervention 4: Placebo
Intervention descriptions: intervention 1: elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days intervention 2: elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days intervention 3: elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days intervention 4: placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days

Protocol document: