Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects with Primary Mitochondrial Disease Resulting from Pathogenic Nuclear DNA Mutations (nPMD)
- Conditions
- MedDRA version: 20.0Level: HLGTClassification code 10052635Term: Cytoplasmic disorders congenitalSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]MedDRA version: 20.0Level: SOCClassification code 10010331Term: Congenital, familial and genetic disordersSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 20.0Level: HLTClassification code 10052637Term: Genetic mitochondrial abnormalities NECSystem Organ Class: 10010331 - Congenital, familial and genetic disordersPrimary Mitochondrial Disease Resulting from Pathogenic Nuclear DNA Mutations (nPMD)
- Registration Number
- EUCTR2021-003907-16-HU
- Lead Sponsor
- Stealth BioTherapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 130
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 administration of assigned treatment.
3. Is =18 years 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 mutations), 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 one 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 98
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32
1. Subject 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 < 200 meters or > 450 meters during the 6MWT (Screening visit only).
4. The estimated glomerular filtration rate (eGFR) is < 30 mL/min/1.73 m2, using the Modification of Diet in Renal Disease (MDRD) Study equation (Screening visit only).
5. Subject has undergone an in-patient hospitalization within 30 days prior to screening or has a planned hospitalization or a surgical procedure during the trial, unless in the opinion of the Investigator it is concluded that it will not impact the outcome measurements of the trial.
6. Subject has clinically significant respiratory disease and/or cardiac disease that would interfere with trial assessments, in the opinion of the Investigator.
7. Subject has had any prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to screening.
8. Subject has history of or current severe neurologic impairment, severe epilepsy, severe ataxia, or severe neuropathy that may interfere with their ability to complete all trial requirements, in the opinion of the Investigator.
9. Active malignancy or any other cancer from which the subject has been disease-free for < 2 years. Localized squamous or non-invasive basal cell skin carcinomas are allowed, if appropriately treated prior to screening.
10. Subject has had a solid organ transplant.
11. Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
12. Subject has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000 cells x106/L at the Screening Visit.
13. 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 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. Subject has received elamipretide (MTP-131) within the past one year of the Screening Visit.
15. Subject has a history of active substance abuse during the year prior, in the opinion of the Investigator.
16. 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 assessments and requirements to the best of their ability.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the effect of single daily SC administration of elamipretide for 48 weeks on the:<br>- Distance walked (in meters) on the 6-Minute Walk Test (6MWT);Secondary Objective: • To evaluate the effect of single daily SC administration of elamipretide for 48 weeks as measured by changes in the:<br>- Total time (in seconds) the Five-Times Sit-to-Stand Test (5XSST)<br>- Total time (in seconds) the Triple Timed Up-and-Go Test (3TUG)<br>- Patient Global Impression (PGI) of Change Scale<br><br>• To evaluate the safety and tolerability of single daily SC doses of elamipretide administered for 48 weeks;Primary end point(s): • To evaluate the effect of single daily SC doses of elamipretide administered for 48 weeks on the:<br>- Distance walked (in meters) on the 6MWT;Timepoint(s) of evaluation of this end point: 6MWT: At all clinical site visits (Screening; Day 1; Week 12; Week 24; Week 36; Week 48; EOT)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • To evaluate the effect of single daily SC doses of elamipretide administered for 48 weeks on the:<br>- Total time (in seconds) on the Five Times Sit-to-Stand Test (5XSST)<br>- Total time (in seconds) on the Triple Timed Up-and-Go Test (3TUG)<br>- Patient Global Impression of Change (PGI) of Change Scale;Timepoint(s) of evaluation of this end point: 3TUG, 5XSST, PGI Tests: At all study site visits (Screening; Day 1; Week 12; Week 24; Week 36; Week 48; EOT)<br>