Primary Mitochondrial Myopathy MedDRA version: 20.0 Level: PT Classification code 10027710 Term: Mitochondrial myopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Sponsors
Stealth BioTherapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide a signed 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 the use of the elamipretide delivery system. 3. Subject is =16 and =80 years of age. In Germany, subjects must be = 18 years of age. 4. Enrolled (signed ICF) in SPIMM-300 or have prior approval from the Sponsor to enroll without SPIMM-300 participation. 5. Diagnosed with PMM in the opinion of the Investigator, consisting of: a. Molecular genetic abnormality of the mitochondrial respiratory chain, and b. Subject reported symptoms (i.e., exercise intolerance, fatigue, muscle weakness) or physical examination findings of myopathy that are the predominant symptoms of the subject’s mitochondrial respiratory chain disorder. 6. The subject’s molecular genetic abnormality is consistent with PMM as confirmed by the Adjudication Committee. 7. 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). 8. Male subjects with female partners of child-bearing 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. PART 2 Subject Continuation Criteria A subject must meet all of the following PART 2 Continuation Criteria at the Week 24 Visit in PART 1 to be eligible for PART 2: 1. Subjects must continue to be able and willing to adhere to the trial requirements. 2. Subject is appropriate to continue in PART 2 (i.e. subject was compliant in SPIMM-301), in the opinion of the Investigator. 3. Subject has not had a serious adverse event (SAE)/serious adverse device effect (SADE) attributed to the elamipretide delivery system. 4. Subject has not permanently discontinued the elamipretide delivery system. Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 194 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Subject has myopathic signs and/or symptoms due to a neuropathic process (i.e. cerebellar dysfunctions and peripheral neuropathies) or a gait problem that would interfere with the 6MWT, in the opinion of the Investigator. 2. Female subjects who are pregnant, planning to become pregnant, or breastfeeding/lactating. 3. Walks 450 meters during the 6MWT at either the Screening Visit OR Baseline Visit. 4. At the Baseline Visit, the estimated glomerular filtration rate (eGFR) 450 msec in male subjects and >480 msec in female subjects. Note: At the initial electrocardiogram (ECG), if QTc exceeds these parameters, the ECG may be repeated 2 more times (during the same visit), and the average of the 3 QTc values used to determine the subject’s eligibility. 8. ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following: a. First degree AV-block b. Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type) c. Right bundle branch block 9. Subject has severe vision impairment that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements 10. Subject has a seizure disorder that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements. 11. Active malignancy or any other cancer from which the subject has been disease-free for 1,000 cells x106/L at the Screening Visit. 15. 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 to the results of the current trial (e.g. exercise therapy trial). 16. Subject has previously received elamipretide (MTP-131), for any reason. 17. Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator. 18. Subject has any prior or current medical condition that, in the judgment of the Investigator, would prevent the subject f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of PART 1 is to evaluate the effect of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for 24 weeks on the: • Distance Walked on the 6MWT • Total Fatigue on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) The PART 2 objective is 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.;Secondary Objective: Secondary objectives of PART 1 are: • To evaluate the effect of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for 24 weeks as measured by changes in the: - Fatigue During Activities on the PMMSA - Neuro-QoL Short Form Fatigue - Most bothersome symptom on the PMMSA - Neuro-QoL Fatigue activities of daily living (specific items from the Neuro-QoL Item Bank). • To evaluate the safety and tolerability of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for 24 weeks.;Primary end point(s): The primary (efficacy) endpoints are: • Distance walked (meters) during the 6MWT • Total Fatigue score on the PMMSA Efficacy will only be assessed for PART 1.;Timepoint(s) of evaluation of this end point: The primary time point is at Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: • Fatigue During Activities score on the PMMSA • Neuro-QoL Fatigue Short Form score • Most bothersome symptom score on the PMMSA • Neuro-QoL Fatigue activities of daily living (specific items from the Neuro-QoL Item Bank);Timepoint(s) of evaluation of this end point: At 24 weeks | — |
Countries
Canada, Denmark, Germany, Hungary, Italy, United Kingdom, United States
Contacts
Public ContactDirector, Clinical Operations
Stealth BioTherapeutics Inc.
Outcome results
None listed