A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension (MMPOWER-3)
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| ClinicalTrials.gov Identifier: NCT03323749 |
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Recruitment Status :
Terminated
(Part1,double blind portion of the trial did not meet the primary end points)
First Posted : October 27, 2017
Results First Posted : April 2, 2021
Last Update Posted : January 24, 2022
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Sponsor:
Stealth BioTherapeutics Inc.
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.
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Brief Summary:
This is a multicenter phase 3 randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the safety and efficacy of daily subcutaneous injections of elamipretide in subjects with primary mitochondrial myopathy. This will be followed by an open-label treatment extension.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Primary Mitochondrial Myopathy | Combination Product: elamipretide Combination Product: placebo comparator Combination Product: elamipretide open label treatment | Phase 3 |
Part 11 is a 24-week, randomized, double-blind, parallel-group, placebo-controlled assessment of the efficacy and safety of single daily subcutaneous (SC) doses of 40 mg elamipretide (vs placebo) administered with the elamipretide delivery system as a treatment for subjects with primary mitochondrial myopathy (PMM). Part 2 was 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 218 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Treatment Extension |
| Actual Study Start Date : | October 9, 2017 |
| Actual Primary Completion Date : | February 10, 2020 |
| Actual Study Completion Date : | February 10, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Myoclonic epilepsy with ragged-red fibers
MedlinePlus related topics:
Muscle Disorders
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1: Elamipretide
40 mg (0.5mL) elamipretide subcutaneous (SC) daily
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Combination Product: elamipretide
40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
Other Name: MTP-131 |
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Placebo Comparator: Part 1: Placebo
Placebo SC daily
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Combination Product: placebo comparator
40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
Other Name: Placebo |
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Experimental: Part 2: Elamipretide open label
Elamepretide 40 mg (0.5 mL) SC daily
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Combination Product: elamipretide open label treatment
40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system |
Primary Outcome Measures :
- Six-minute Walk Test (6MWT) [ Time Frame: Baseline to 24 weeks ]Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
- Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) [ Time Frame: Baseline to 24 weeks ]Change from Baseline in Total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) by visit. Each individual item score ranges from 1 (none) to 4 (severe). The total fatigue score ranges from 4-16. Lower values represent a better outcome. The total fatigue score is the sum of question 1 through question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.
Secondary Outcome Measures :
- Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA). [ Time Frame: Baseline to 24 weeks ]Change from baseline in Fatigue During Activities. Fatigue During Activities is the sum of question 2 (tiredness during activities) and question 4 (muscle weakness during activities.) The four response options are: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Raw scores for each subject range from 2-8. A lower score means a better outcome, with less fatigue. A higher score means a worse outcome, with more fatigue.
- Neuro-QoL Fatigue Activities of Daily Living [ Time Frame: Baseline to 24 weeks ]Change From Baseline in Neuro-QoL Fatigue Activities of Daily Living by Visit. Each individual item score ranges from 1-5. Total raw score for the entire item bank ranges from 19-95. Raw scores will be calibrated using Item Response Theory Model. Lower values represent a better outcome. Individual items will be summed to calculate total scores.
- Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment [ Time Frame: Baseline to 24 weeks ]The item score rangers from 1 (none) to 4 (severe). Lower values represent a better outcome. The most bothersome score is the average of the identified most bothersome symptom of the Primary Mitochondrial Myopathy Symptom Assessment by each subject.
- Neuro-QoL Fatigue Short Form Score [ Time Frame: 24 Weeks ]Change From Baseline in Neuro-QoL Fatigue - Short Form: Total T-Scores by Visit. The Neuro-QoL Fatigue Short Form is comprised of the sum of the first 8 questions of the Neuro-QoL Item Bank v1.0 - Fatigue. Each question is scored as following: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always. The questions include: I felt exhausted, I felt that I had no energy, I felt fatigued, I was too tired to do my household chores, I was too tired to leave the house, I was frustrated by being too tired to do the things I wanted to do, I felt tired, and I had to limit my social activity because I was tired. T-scores are calculated from the short form scoring table provided by the instrument authors (Neuro-QoL User Manual, 2015). T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Change from baseline: Negative numbers mean less fatigue, better outcome, positive score means more fatigue, worse outcome.
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| Ages Eligible for Study: | 16 Years to 80 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
PART 1:
Inclusion Criteria:
- Willing and able to provide a signed informed consent form prior to participation in any trial-related procedures
- Agrees to adhere to the trial requirements for the length of the trial, including the use of the elamipretide delivery system
- Subject is ≥ 16 and ≤ 80 years of age
- Diagnosed with PMM in the opinion of the investigator and confirmed by an Adjudication Committee
- Woman of childbearing potential must agree to use a highly effective method of birth control
Exclusion Criteria:
- Subject has myopathic signs and or/symptoms due to a neuropathic process or gait problem that would interfere with the 6 minute walk test (6MWT), in the opinion of the Investigator
- Female who are pregnant, planning to become pregnant, or breastfeeding/lactating
- At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
- 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.
- 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.
- 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.
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ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following:
- First degree Atrioventricular bock (AV-block)
- Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
- Right bundle branch block
- Subject has severe vision impairment that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements
- Subject has a seizure disorder that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements.
- Active malignancy or any other cancer from which the subject has been disease-free for < 2 years.
- Subject has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression, in the opinion of the Investigator.
- Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
- Subject has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000 cells x10^6/L at the Screening Visit.
- 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 with results of the current trial (e.g., exercise therapy trial).
- Subject has previously received elamipretide (MTP-131), for any reason.
- Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator.
- 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.
PART 2:
Continuation Criteria:
- Subjects must continue to be able and willing to adhere to the trial requirements.
- Subject is appropriate to continue in Part 2 (i.e. subject was compliant in Part 1), in the opinion of the Investigator.
- Subject has not had a serious adverse event (SAE)/serious adverse device effect (SADE) attributed to the elamipretide delivery system.
- Subject has not permanently discontinued the elamipretide delivery system.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03323749
Locations
Show 27 study locations
Sponsors and Collaborators
Stealth BioTherapeutics Inc.
Study Documents (Full-Text)
Documents provided by Stealth BioTherapeutics Inc.:
Documents provided by Stealth BioTherapeutics Inc.:
Study Protocol [PDF] June 15, 2018
Statistical Analysis Plan [PDF] November 29, 2019
| Responsible Party: | Stealth BioTherapeutics Inc. |
| ClinicalTrials.gov Identifier: | NCT03323749 |
| Other Study ID Numbers: |
SPIMM-301 |
| First Posted: | October 27, 2017 Key Record Dates |
| Results First Posted: | April 2, 2021 |
| Last Update Posted: | January 24, 2022 |
| Last Verified: | January 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Stealth BioTherapeutics Inc.:
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Myopathy PMD Primary Mitochondrial Disease MTP-131 elamipretide |
Additional relevant MeSH terms:
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Muscular Diseases Mitochondrial Myopathies Musculoskeletal Diseases Neuromuscular Diseases |
Nervous System Diseases Mitochondrial Diseases Metabolic Diseases |