Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy

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.

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).

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of mitochondrial disease believed to impair the mitochondrial respiratory chain.
* Eligibility requires prior genetic confirmation of mitochondrial disease.
* Diagnosis of mitochondrial myopathy judged by the Investigators to be due to existing mitochondrial disease.
* Must be able to complete a Screening Visit 6MWT.
* Body mass index (BMI) score \>15.0 and \<35.0 kg/m2 at Screening Visit.
* Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the ICF until two months after the last dose of study drug.

Exclusion Criteria:

* 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.
* Had any exclusionary Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores at Screening Visit.
* Hospitalized (admitted as in-patient) within 1 month prior to the Baseline Visit.
* A history of type 1 diabetes mellitus (T1DM).
* Uncontrolled Type 1 (T1DM) or Type 2 diabetes mellitus (T2DM), in the opinion of the investigator.
* A creatinine clearance \<45 mL/min as calculated by the Cockcroft Gault equation.
* Requires pacemaker, defibrillator, or has undergone cardiac surgery within 2 years of Screening Visit.
* QTc elongation defined as a QTc \>450 msec in male subjects and \>480 msec in female subjects.
* Uncontrolled hypertension (\>160 mmHg systolic or \>100 mmHg diastolic) at Screening Visit.
* History of rhabdomyolysis defined as an acute rise in the serum creatine phosphokinase (CPK) value that, in the opinion of the investigator, caused clinically significant symptoms.
* Serum sodium more than 5 meq/L below the reference lower limit of normal at Screening Visit.
* Participated in another interventional clinical trial within 3 months of the screening visit or is currently enrolled in a non-interventional clinical trial judged by the Investigator to be incompatible with the current trial.

  * Other protocol-defined inclusion/exclusion criteria may apply.