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

Primary Purpose

Primary Mitochondrial Myopathy

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
elamipretide
placebo comparator
elamipretide open label treatment
Sponsored by
Stealth BioTherapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Mitochondrial Myopathy focused on measuring Myopathy, PMD, Primary Mitochondrial Disease, MTP-131, elamipretide

Eligibility Criteria

16 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California San Diego
  • Stanford University
  • Children's Hospital Colorado
  • Rare Disease Research, LLC
  • Massachusetts General Hospital
  • Columbia University Medical Center
  • Akron Children's Hospital
  • Cleveland Clinical Neurological Institute
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • Baylor College of Medicine/Texas Children's Hospital
  • University of Texas Health Science Center
  • Seattle Children's Hospital
  • Adult Metabolic Diseases Clinic
  • McMaster University Medical Center
  • Copenhagen Neuromuscular Center
  • University Hospital of Bonn
  • Klinikum der Universität München, Friedrich-Baur Institute
  • Institute of Genomic Medicine and Rare Disorders
  • IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital
  • Azienda Ospedaliero Universitaria Policlinico G. Martino
  • Istituto Nazionale Neurologico Carlo Besta
  • Dipartimento Ambientale di Neuroscienze
  • Ospedale Pediatrico Bambin Gesù
  • Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli
  • MRC Centre for Neuromuscular Diseases
  • Royal Victoria Infirmary

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1: Elamipretide

Part 1: Placebo

Part 2: Elamipretide open label

Arm Description

40 mg (0.5mL) elamipretide subcutaneous (SC) daily

Placebo SC daily

Elamepretide 40 mg (0.5 mL) SC daily

Outcomes

Primary Outcome Measures

Six-minute Walk Test (6MWT)
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)
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).
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
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
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
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.

Full Information

First Posted
October 12, 2017
Last Updated
January 16, 2022
Sponsor
Stealth BioTherapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03323749
Brief Title
A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension
Acronym
MMPOWER-3
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Part1,double blind portion of the trial did not meet the primary end points
Study Start Date
October 9, 2017 (Actual)
Primary Completion Date
February 10, 2020 (Actual)
Study Completion Date
February 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stealth BioTherapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mitochondrial Myopathy
Keywords
Myopathy, PMD, Primary Mitochondrial Disease, MTP-131, elamipretide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
218 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Elamipretide
Arm Type
Experimental
Arm Description
40 mg (0.5mL) elamipretide subcutaneous (SC) daily
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo SC daily
Arm Title
Part 2: Elamipretide open label
Arm Type
Experimental
Arm Description
Elamepretide 40 mg (0.5 mL) SC daily
Intervention Type
Combination Product
Intervention Name(s)
elamipretide
Other Intervention Name(s)
MTP-131
Intervention Description
40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
Intervention Type
Combination Product
Intervention Name(s)
placebo comparator
Other Intervention Name(s)
Placebo
Intervention Description
40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
Intervention Type
Combination Product
Intervention Name(s)
elamipretide open label treatment
Intervention Description
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 Measure Information:
Title
Six-minute Walk Test (6MWT)
Description
Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
Time Frame
Baseline to 24 weeks
Title
Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
Description
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.
Time Frame
Baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).
Description
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.
Time Frame
Baseline to 24 weeks
Title
Neuro-QoL Fatigue Activities of Daily Living
Description
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.
Time Frame
Baseline to 24 weeks
Title
Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment
Description
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.
Time Frame
Baseline to 24 weeks
Title
Neuro-QoL Fatigue Short Form Score
Description
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.
Time Frame
24 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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. 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.
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rare Disease Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cleveland Clinical Neurological Institute
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Baylor College of Medicine/Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Adult Metabolic Diseases Clinic
City
Vancouver
State/Province
British Colombia
Country
Canada
Facility Name
McMaster University Medical Center
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Copenhagen Neuromuscular Center
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
University Hospital of Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Klinikum der Universität München, Friedrich-Baur Institute
City
Munich
ZIP/Postal Code
80336
Country
Germany
Facility Name
Institute of Genomic Medicine and Rare Disorders
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Policlinico G. Martino
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Istituto Nazionale Neurologico Carlo Besta
City
Milan
ZIP/Postal Code
20133
Country
Italy
Facility Name
Dipartimento Ambientale di Neuroscienze
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Ospedale Pediatrico Bambin Gesù
City
Rome
ZIP/Postal Code
00165
Country
Italy
Facility Name
Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
MRC Centre for Neuromuscular Diseases
City
London
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle Upon Tyne
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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