A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension

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

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.

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.

PART 1:

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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:

  1. First degree Atrioventricular bock (AV-block)
  2. Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
  3. 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.

PART 2:

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.