A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension (MMPOWER-3)

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

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.

Study Overview

• Status: Terminated
• Conditions: Primary Mitochondrial Myopathy
• Intervention / Treatment: Combination product: elamipretide; Combination product: placebo comparator; Combination product: elamipretide open label treatment

Detailed Description

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
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Colombia
    • Vancouver, British Colombia, Canada
      • Adult Metabolic Diseases Clinic
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University Medical Center
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Copenhagen neuromuscular center
• Germany
  • Bonn, Germany, 53105
    • University Hospital of Bonn
  • Munich, Germany, 80336
    • Klinikum der Universität München, Friedrich-Baur Institute
• Hungary
  • Budapest, Hungary, 1083
    • Institute of Genomic Medicine and Rare Disorders
• Italy
  • Bologna, Italy, 40139
    • IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital
  • Messina, Italy, 98125
    • Azienda Ospedaliero Universitaria Policlinico G. Martino
  • Milan, Italy, 20133
    • Istituto Nazionale Neurologico Carlo Besta
  • Pisa, Italy, 56126
    • Dipartimento Ambientale di Neuroscienze
  • Rome, Italy, 00165
    • Ospedale Pediatrico Bambin Gesù
  • Rome, Italy, 00168
    • Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli
• United Kingdom
  • London, United Kingdom
    • MRC Centre for Neuromuscular Diseases
  • Newcastle Upon Tyne, United Kingdom
    • Royal Victoria Infirmary
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinical Neurological Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

• ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following:

  1. First degree Atrioventricular bock (AV-block)
  2. Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Elamipretide; 40 mg (0.5mL) elamipretide subcutaneous (SC) daily	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 Names: MTP-131
Placebo Comparator: Part 1: Placebo; Placebo SC daily	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 Names: Placebo
Experimental: Part 2: Elamipretide open label; Elamepretide 40 mg (0.5 mL) SC daily	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six-minute Walk Test (6MWT)	Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit	Baseline to 24 weeks
Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)	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.	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).	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.	Baseline to 24 weeks
Neuro-QoL Fatigue Activities of Daily Living	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.	Baseline to 24 weeks
Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment	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.	Baseline to 24 weeks
Neuro-QoL Fatigue Short Form Score	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.	24 Weeks

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): February 10, 2020
• Study Completion (Actual): February 10, 2020

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 16, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: PMD; MTP-131; Myopathy; Primary Mitochondrial Disease; elamipretide
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Mitochondrial Diseases; Muscular Diseases; Mitochondrial Myopathies
• Other Study ID Numbers: SPIMM-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No