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A subject must meet all of the following inclusion criteria at the Screening |
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and Baseline Visit (unless otherwise specified) to be eligible for inclusion |
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in the SPIMD-301 trial: 1\. Willing and able to provide a signed informed |
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consent form (ICF) prior to participation in any trial-related procedures. 2\ |
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Agrees and is able to adhere to the trial requirements for the length of the |
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trial, including administration of assigned treatment. 3\. Is ≥18 years and ≤ |
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years of age at the time of screening. 4\. Diagnosed with nPMD with a |
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predominant clinical manifestation of myopathy, which must include progressive |
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external ophthalmoplegia (PEO) and exercise intolerance and/or skeletal muscle |
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weakness, with genetic confirmation of either: 1\. Nuclear DNA mutation of the |
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mitochondrial replisome (replisome-related mutations), which include the |
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following genes: \- POLG 1/2 \- TWINKLE (C10ORF2) \- TYMP \- DGUOK \- TK2 \- |
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RRM2B \- RNASEH1 \- SSBP \- MGME1 \- DNA2 \- ANT1 (SLC25A4) \- SUCLG1 \- |
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SUCLA2 \- MPV17 or 2\. Other pathogenic mutations specific to nuclear DNA. 5\ |
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Women of childbearing potential must agree to use one of the following methods |
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of birth control from the date they sign the ICF until 28 days after the last |
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dose of IMP: 1\. Abstinence, when it is in line with the preferred and usual |
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lifestyle of the subject. Subject agrees to use a highly effective method of |
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contraception should they become sexually active. 2\. Relationships with male |
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partners who have been surgically sterilized by vasectomy (the vasectomy |
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procedure must have been conducted at least 60 days prior to the Screening |
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Visit). 3\. Barrier method (e.g., condom or occlusive cap) with spermicidal |
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injectable) or an intrauterine device or system. Note: Non-childbearing |
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potential is defined as surgical sterilization (e.g., bilateral oophorectomy |
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hysterectomy, or tubal ligation) or postmenopausal (defined as permanent |
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cessation of menstruation for at least 12 consecutive months prior to the |
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Screening Visit). 6\. Male subjects with female partners of childbearing |
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potential must be willing to use a highly effective method of contraception |
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from the date they sign the ICF until 28 days after the last dose of IMP |
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foam/gel/film/cream AND either hormonal contraception (oral, implanted, or |
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\. Is unable to perform the 6MWT, 3TUG, or 5XSST
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functional tests. The use of a gait assist device is allowed; however, use
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should remain consistent for the entire duration of the trial. 2\. Female
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subjects who are pregnant, planning to become pregnant, or
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breastfeeding/lactating. 3\. Walks < 150 meters or > 450 meters during the
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MWT (Screening Visit only). 4\. The estimated glomerular filtration rate
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(eGFR) is < 30 mL/min/1.73 m2, using the Modification of Diet in Renal Disease
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(MDRD) Study equation (Screening Visit only). 5\. Has undergone an in-patient
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hospitalization within 30 days prior to screening or has a planned
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hospitalization or a surgical procedure during the trial, unless, in the
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opinion of the Investigator, it is concluded that it will not impact the
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outcome measurements of the trial. 6\. Has clinically significant respiratory
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disease and/or cardiac disease that would interfere with trial assessments, in
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the opinion of the Investigator. 7\. Has had any prior interventional cardiac
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procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary
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intervention, balloon valvuloplasty, etc.) within 3 months prior to screening
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\. Has history of or current severe neurologic impairment, severe epilepsy
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severe ataxia, or severe neuropathy that may interfere with their ability to
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complete all trial requirements, in the opinion of the Investigator. 9\
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Active malignancy or any other cancer from which the subject has been disease-
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free for < 2 years. Localized squamous or non-invasive basal cell skin
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carcinomas are allowed, if appropriately treated prior to screening. 10\. Has
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had a solid organ transplant. 11\. Has been previously diagnosed with human
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immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 12\. Has
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a history of a systemic eosinophilic illness and/or an eosinophil count >1,000
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cells x106/L at the Screening Visit. 13\. Is currently participating or has
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participated in an interventional clinical trial (i.e., investigational
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product or device, stem cell therapy, gene therapy) within 30 days prior to
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current trial; or is currently enrolled in a non-interventional clinical trial
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that, in the opinion of the Investigator, may be potentially confounding to
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the results of the current trial (e.g., exercise therapy trial). 14\. Has
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received elamipretide (MTP-131) within the past one year of the Screening
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Visit. 15\. Has a history of active substance abuse during the year prior, in
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the opinion of the Investigator
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