Primary mitochondrial disease resulting from pathogenic nuclear DNA mutations. Congenital, familial and genetic disorders. Cytoplasmic disorders congenital. Genetic mitochondrial abnormalities NEC. energy metabolism disease nuclear Primary Mitochondrial Disease (nPMD)
Conditions
Interventions
Subjects will be randomized (in a ratio of 1:1) to one of two groups:
- 48 weeks of single daily SC doses of 60 mg elamipretide (MTP-131) or
- 48 weeks of single daily SC doses of placebo.
Subjects r
Sponsors
Stealth BioTherapeutics Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Willing and able to provide a signed and dated informed consent form (ICF) prior to participation in any trial-related procedures. 2. Agrees, and is able, to adhere to the trial requirements for the length of the trial, including administration of assigned treatment. 3. Is between 18 and 70 years of age at the time of screening. 4. Diagnosed with nPMD with a predominant clinical manifestation of myopathy, which must include progressive external ophthalmoplegia (PEO) and exercise intolerance and/or skeletal muscle weakness, with genetic confirmation of either: a. Nuclear DNA mutation of the mitochondrial replisome (replisome-related mutation), which include the following genes: POLG 1/2; TWINKLE (C10ORF2); TYMP; DGUOK; TK2; RRM2B; RNASEH1; SSBP; MGME1; DNA2; ANT1 (SLC25A4); SUCLG1; SUCLA2; MPV17 or b. other pathogenic mutations specific to nuclear DNA. 5. Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until 28 days after the last dose of IMP: a. abstinence, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use a highly effective method of contraception should they become sexually active. b. Relationships with male partners who have been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit). c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system. Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit). 6. Male subjects with female partners of childbearing potential must be willing to use a highly effective method of contraception from the date they sign the ICF until 28 days after the last dose of IMP.
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Is unable to perform the 6MWT, 3TUG, or 5XSST functional tests. The use of a gait assist device is allowed; however, use should remain consistent for the entire duration of the trial. 2. Female subjects who are pregnant, planning to become pregnant, or breastfeeding/lactating. 3. Walks 450 meters during the 6MWT (screening visit only). 4. The estimated glomerulal filtration rate (eGFR) is 1,000 cells x106/L at the Screening Visit. 13. 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 prior to current trial; or is currently enrolled in a non-interventional clinical trial that, in the opinion of the Investigator, may be potentially confounding to the results of the current trial (e.g., exercise therapy trial). 14. Has received elamipretide (MTP-131) within the past one year of the Screening Visit. 15. Has a history of active substance abuse during the year prior, in the opinion of the Investigator. 16. 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 assessments and requirements to the best of their ability. 17. Has a history of allergic reaction to the investigational drug or any of its components.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the effect of single daily SC administration of elamipretide for 48 weeks on the: - Distance walked (in meters) on the 6-Minute Walk Test (6MWT) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: To evaluate the effect of single daily SC administration of elamipretide for 48 weeks on the: - Total time (in seconds) the Five-Times Sit-to-Stand Test (5XSST) - Total time (in seconds) the Triple Timed Up-and-Go Test (3TUG) - Patient Global Impression of Severity (PGI-S) Scale | — |
Countries
Netherlands
Outcome results
None listed