A Phase 3 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled 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
- Primary mitochondrial disease resulting from pathogenic nuclear DNA mutations. Congenital, familial and genetic disorders. Cytoplasmic disorders congenital. Genetic mitochondrial abnormalities NEC.energy metabolism diseasenuclear Primary Mitochondrial Disease (nPMD)10028396
- Registration Number
- NL-OMON51595
- Lead Sponsor
- Stealth BioTherapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
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.
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 < 150 meters or >450 meters during the 6MWT (screening visit only).
4. The estimated glomerulal 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. 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. Has clinically significant respiratory disease and/or cardiac disease that
would
interfere with trial assessments, in the opinion of the Investigator.
7. 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. 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. Has had a solid organ transplant.
11. Has been previously diagnosed with human immunodeficiency virus (HIV),
hepatitis
B, or hepatitis C infection.
12. Has a history of a systemic eosinophilic illness and/or an eosinophil count
>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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the effect of single daily SC administration of elamipretide for 48<br /><br>weeks on the:<br /><br>- Distance walked (in meters) on the 6-Minute Walk Test (6MWT)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints:<br /><br>To evaluate the effect of single daily SC administration of elamipretide for 48<br /><br>weeks on the:<br /><br>- Total time (in seconds) the Five-Times Sit-to-Stand Test (5XSST)<br /><br>- Total time (in seconds) the Triple Timed Up-and-Go Test (3TUG)<br /><br>- Patient Global Impression of Severity (PGI-S) Scale</p><br>