E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Mitochondrial Myopathy |
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E.1.1.1 | Medical condition in easily understood language |
Primary Mitochondrial Myopathy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027710 |
E.1.2 | Term | Mitochondrial myopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 Fatigue - Most bothersome symptom on the PMMSA • To evaluate the safety and tolerability of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for 24 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 4. Enrolled (signed ICF) in SPIMM-300. 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 in SPIMM-300. 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 trial completion: 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 trial completion.
PART 2 Subject Continuation Criteria A subject must meet all of the following PART 2 Continuation Criteria at the Week 24 Visit in SPIMM-301 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. |
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E.4 | Principal exclusion criteria |
1. Subject has myopathic signs and/or symptoms due to a neuropathic process (i.e. cerebellar dysfunctions and 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 < 100 meters or > 450 meters during the 6MWT at either the Screening Visit OR Baseline Visit. 4. At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, using the Modification of Diet in Renal Disease (MDRD) Study equation. 5. Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial. 6. Subject has clinically significant cardiac disease or prior interventional procedure and/or respiratory disease (medical history or current clinical findings) within 3 months of the Baseline Visit, in the opinion of the Investigator. 7. Subject has QTc elongation (using the correction factor utilized at the clinical site) defined as a QTc >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 < 2 years. 12. Subject has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression, in the opinion of the Investigator. 13. Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 14. Subject has a history of a systemic eosinophilic illness and/or an eosinophil count >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 from safely participating in and/or completing all trial requirements. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary time point is at Week 24. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: • Fatigue During Activities score on the PMMSA • Neuro-QoL Fatigue score • Most bothersome symptom score on the PMMSA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Denmark |
Germany |
Hungary |
Italy |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |