a trial to evaluate safety and efficacy of elamipretide primary mitochondrial myopathy followed by open-label extension

Conditions: Primary Mitochondrial Myopathy

Summary: 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.

Eligibility criteria:
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.

Keywords: myopathy pmd primary mitochondrial disease mtp-131 elamipretide