Back to resultsSafety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study (MMPOWER-2)
Primary Purpose
Primary Mitochondrial Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Elamipretide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Primary Mitochondrial Disease focused on measuring Primary Mitochondrial Disease, Mitochondrial Myopathy, Elamipretide, MTP-131, Bendavia™
Eligibility Criteria
Inclusion Criteria:
- Subject completed participation in the SPIMM-201 study without a significant protocol deviation that would suggest the subject may not be able to complete all study requirements in the opinion of the Sponsor
- Subject must reside in North America for the duration of the study
- Subject has not received study drug in the SPIMM-201 study within 3 weeks prior to Screening
- Women of childbearing potential must agree to use 1 of the methods of birth control specified in the protocol from the date they sign the informed consent form (ICF) until two months after the last dose of study drug
- Subject has been on stable (unchanged and constant) medications (including over-the counter treatments, vitamins, or supplements) for at least 1 month prior to the Baseline Visit
Exclusion Criteria:
- 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 study requirements (i.e. unstable angina or recent myocardial infarction)
- Subject has received any investigational compound and/or has participated in another interventional clinical study within 30 days prior to the Baseline Visit or is concurrently enrolled in any non-interventional research of any type judged to be scientifically or medically incompatible with the study as deemed by the Investigator in consultation with the Sponsor
- Subject experienced an adverse reaction to study drug in the SPIMM-201 study that contraindicates further treatment with elamipretide in the opinion of the Investigator and/or Sponsor
- Female subjects who are pregnant, planning to become pregnant, or lactating
- Subject has undergone an in-patient hospitalization within the 1 month prior to the Screening Visit or is likely to need in-patient hospitalization or a surgical procedure during the course of the study
- Subject has a creatinine clearance ≤30 mL/min as calculated by the Cockcroft Gault equation
- Subject has a corrected QT interval (QTc) elongation defined as a QTc >450 msec in male subjects and >480msec in female subjects. Note: At the initial electrocardiogram (ECG), if QTc exceeds these parameters, the ECG may be repeated 2 more times, and the average of the 3 QTc values used to determine the subjects eligibility
- Subject has uncontrolled hypertension in the judgment of the Investigator (e.g. elevated above >160 mmHg systolic or >100 mmHg diastolic despite appropriate treatment on two consecutive readings)
- Subject has a history of clinically significant hypersensitivity or allergy to any of the excipients contained in the study drug
- Subject has a history of active alcoholism or drug addiction during the year before the Screening Visit
Sites / Locations
- University of California
- Massachusetts General Hospital
- Akron Children's Hospital
- Children's Hospital of Pittsburg of UPMC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Elamipretide, Then Placebo
Placebo, Then Elamipretide
Arm Description
Participants first received 40 mg of elamipretide once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received placebo administered once daily subcutaneously for 4 weeks.
Participants first received placebo once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received 40 mg of elamipretide once daily subcutaneously for 4 weeks.
Outcomes
Primary Outcome Measures
Distance Walked on the 6-minute Walk Test (6MWT) by Visit
Distance in meters walked on the 6-minute walk test (6MWT) at end of treatment, where end of treatment means end of week 4 for Period 1 and end of week 12 for Period 2.
Secondary Outcome Measures
Wrist Accelerometer Counts by Day
Wrist Accelerometer Counts by the last 7 days prior to the date of the end of treatment visit; End of treatment being end of Week 4 for Treatment Period 1 and end of Week 12 for Treatment Period 2. Subjects wore an activity monitor, or wrist accelerometer, on their wrist daily (from the Screening Visit to the End-of-Study/Early Discontinuation Visit). As a measure of physical activity and mobility, subjects wore an activity monitor, or wrist accelerometer, which measured mean vector magnitude of accelerations per daywith higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data were used for the analysis of as the vector magnitude of the wrist data.
Average Hip Accelerator Counts by Day
Average Hip Accelerator Counts by last 7 days predose, and prior to end of treatment; End of treatment being Week 4 for Treatment Period 1 and Week 12 for Treatment Period 2. As a measure of physical activity and mobility, subjects wore an activity monitor, or hip accelerometer, on their hip (or belt line) daily during waking hours (minimum of at least 7 consecutive days immediately prior to study drug administration in each Treatment Period [Predose; at Visit 2 for Treatment Period 1 and at Visit 4 for Treatment Period 2]), and at the end of each Treatment Period [at Visit 3 for Treatment Period 1 and Visit 5 for Treatment Period 2]), which measured average acceleration per day, with higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data was used for the analysis of mean vertical axis (Y) cou
Neuro-QoL Fatigue Short Form Score: Total T-Scores (Question 1-8)
Participants respond to the following statements of the Quality of Life in Neurological Disorders Fatigue Assessment (Neuro-QOL Fatigue Item Bank at end of treatment: 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; I had to limit my social activity because I was tired.Individual response options range from a score of 1 to 5, where 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always for end of treatment, where end of treatment period is end of week 4 for period 1, and end of week 12 for period 2. Raw scores are calculated as simple summed scores to an Item Response Theory Metric referred to as the T-score metric. Higher T-score means more fatigue, which means a worse outcome, with possible scores ranging from 29.5 to 74.1. Mean population T-score and standard deviation was reported.
Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score by Week
Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue score at end of treatment (sum of Q1 to Q4; tiredness/muscle weakness) is scored as follows: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Total score range is 4-16; lower score means less fatigue and better outcome, higher score means more fatigue and worse outcome. Participants rate the following: Tiredness at rest, Tiredness during activities, Muscle weakness at rest, Muscle weakness during activities, at the end of each treatment period, where end of treatment period is the weekly average of the last 7 days of week 4 for period 1 and the last 7 days of week 12 for period 2.
Triple Timed Up and Go (3TUG) Test by Visit
Participant performed 3TUG test after the 6MWT, and after at least 15 minutes rest prior to study drug administration in each Treatment Period (End of Week 4 for Period 1 and End of Week 12 for Period 2.) Participant was directed to stand up from chair, walk at normal pace to the line on the floor 3 meters away,turn, walk back to the chair at normal pace, sit down again; activity was timed, in seconds. Activity is repeated 3 times consecutively without rest and an average time is calculated.
Patient Global Assessment [PGA] Score by Visit, Continuous
Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome.
Patient Global Assessment by Visit, Categorical
Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.
Physician Global Assessment (PhGA) By Visit, Continuous
Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome.
Physician Global Assessment (PhGA) By Visit, Categorical
Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.
Full Information
NCT ID
NCT02805790
First Posted
June 13, 2016
Last Updated
July 6, 2020
Sponsor
Stealth BioTherapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02805790
Brief Title
Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
Acronym
MMPOWER-2
Official Title
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Crossover Study to Evaluate Safety, Tolerability, and Efficacy of Subcutaneous Injections of MTP-131 in Subjects With Mitochondrial Myopathy Previously Treated in the SPIMM-201 Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 22, 2016 (Actual)
Primary Completion Date
March 10, 2017 (Actual)
Study Completion Date
March 23, 2017 (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 randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (PMM) to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of subcutaneous elamipretide in this patient population.
Detailed Description
This randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (PMM) who had completed participation in the SPIMM-201 study where they had received 5 days of intravenous (IV) elamipretide (0.01, 0.10, or 0.25 mg/kg/hour infused for 2 hours) or placebo (randomized 3:1). The primary objective was to evaluate the effect of single daily subcutaneous (SC) doses of elamipretide administered for 4 weeks on the 6-minute walking distance (6MWD).
Subjects were randomized (1:1) to one of two sequence groups: 4-weeks of treatment with 40 mg elamipretide administered once daily SC in Treatment Period 1 followed by 4-weeks of treatment with placebo administered once daily SC in Treatment Period 2 (separated by a 4-week washout period), or vice versa. Each sequence group went through 5 distinct periods: Screening, Treatment Period 1, Washout, Treatment Period 2, and Follow-Up. Safety, tolerability, pharmacokinetics (PK), and efficacy of subcutaneous elamipretide in this patient population were analyzed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mitochondrial Disease
Keywords
Primary Mitochondrial Disease, Mitochondrial Myopathy, Elamipretide, MTP-131, Bendavia™
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Elamipretide, Then Placebo
Arm Type
Experimental
Arm Description
Participants first received 40 mg of elamipretide once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received placebo administered once daily subcutaneously for 4 weeks.
Arm Title
Placebo, Then Elamipretide
Arm Type
Placebo Comparator
Arm Description
Participants first received placebo once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received 40 mg of elamipretide once daily subcutaneously for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Elamipretide
Other Intervention Name(s)
Bendavia, MTP-131
Intervention Description
4 weeks of treatment with 40 mg elamipretide administered once daily subcutaneously
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
4 weeks of treatment with placebo administered once daily subcutaneously
Primary Outcome Measure Information:
Title
Distance Walked on the 6-minute Walk Test (6MWT) by Visit
Description
Distance in meters walked on the 6-minute walk test (6MWT) at end of treatment, where end of treatment means end of week 4 for Period 1 and end of week 12 for Period 2.
Time Frame
End of Week 4 and End of Week 12
Secondary Outcome Measure Information:
Title
Wrist Accelerometer Counts by Day
Description
Wrist Accelerometer Counts by the last 7 days prior to the date of the end of treatment visit; End of treatment being end of Week 4 for Treatment Period 1 and end of Week 12 for Treatment Period 2. Subjects wore an activity monitor, or wrist accelerometer, on their wrist daily (from the Screening Visit to the End-of-Study/Early Discontinuation Visit). As a measure of physical activity and mobility, subjects wore an activity monitor, or wrist accelerometer, which measured mean vector magnitude of accelerations per daywith higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data were used for the analysis of as the vector magnitude of the wrist data.
Time Frame
Last 7 days prior to the date of end of treatment visit
Title
Average Hip Accelerator Counts by Day
Description
Average Hip Accelerator Counts by last 7 days predose, and prior to end of treatment; End of treatment being Week 4 for Treatment Period 1 and Week 12 for Treatment Period 2. As a measure of physical activity and mobility, subjects wore an activity monitor, or hip accelerometer, on their hip (or belt line) daily during waking hours (minimum of at least 7 consecutive days immediately prior to study drug administration in each Treatment Period [Predose; at Visit 2 for Treatment Period 1 and at Visit 4 for Treatment Period 2]), and at the end of each Treatment Period [at Visit 3 for Treatment Period 1 and Visit 5 for Treatment Period 2]), which measured average acceleration per day, with higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data was used for the analysis of mean vertical axis (Y) cou
Time Frame
Last 7 days prior to the date of end of treatment visit
Title
Neuro-QoL Fatigue Short Form Score: Total T-Scores (Question 1-8)
Description
Participants respond to the following statements of the Quality of Life in Neurological Disorders Fatigue Assessment (Neuro-QOL Fatigue Item Bank at end of treatment: 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; I had to limit my social activity because I was tired.Individual response options range from a score of 1 to 5, where 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always for end of treatment, where end of treatment period is end of week 4 for period 1, and end of week 12 for period 2. Raw scores are calculated as simple summed scores to an Item Response Theory Metric referred to as the T-score metric. Higher T-score means more fatigue, which means a worse outcome, with possible scores ranging from 29.5 to 74.1. Mean population T-score and standard deviation was reported.
Time Frame
End of Week 4 and End of Week 12
Title
Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score by Week
Description
Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue score at end of treatment (sum of Q1 to Q4; tiredness/muscle weakness) is scored as follows: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Total score range is 4-16; lower score means less fatigue and better outcome, higher score means more fatigue and worse outcome. Participants rate the following: Tiredness at rest, Tiredness during activities, Muscle weakness at rest, Muscle weakness during activities, at the end of each treatment period, where end of treatment period is the weekly average of the last 7 days of week 4 for period 1 and the last 7 days of week 12 for period 2.
Time Frame
Last 7 days of Week 4 and Last 7 days of Week 12
Title
Triple Timed Up and Go (3TUG) Test by Visit
Description
Participant performed 3TUG test after the 6MWT, and after at least 15 minutes rest prior to study drug administration in each Treatment Period (End of Week 4 for Period 1 and End of Week 12 for Period 2.) Participant was directed to stand up from chair, walk at normal pace to the line on the floor 3 meters away,turn, walk back to the chair at normal pace, sit down again; activity was timed, in seconds. Activity is repeated 3 times consecutively without rest and an average time is calculated.
Time Frame
End of Week 4 and End of Week 12
Title
Patient Global Assessment [PGA] Score by Visit, Continuous
Description
Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome.
Time Frame
End of Week 4 and End of Week 12
Title
Patient Global Assessment by Visit, Categorical
Description
Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.
Time Frame
End of Week 4 and End of Week 12
Title
Physician Global Assessment (PhGA) By Visit, Continuous
Description
Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome.
Time Frame
End of Week 4 and End of Week 12
Title
Physician Global Assessment (PhGA) By Visit, Categorical
Description
Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.
Time Frame
End of Week 4 and End of Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject completed participation in the SPIMM-201 study without a significant protocol deviation that would suggest the subject may not be able to complete all study requirements in the opinion of the Sponsor
Subject must reside in North America for the duration of the study
Subject has not received study drug in the SPIMM-201 study within 3 weeks prior to Screening
Women of childbearing potential must agree to use 1 of the methods of birth control specified in the protocol from the date they sign the informed consent form (ICF) until two months after the last dose of study drug
Subject has been on stable (unchanged and constant) medications (including over-the counter treatments, vitamins, or supplements) for at least 1 month prior to the Baseline Visit
Exclusion Criteria:
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 study requirements (i.e. unstable angina or recent myocardial infarction)
Subject has received any investigational compound and/or has participated in another interventional clinical study within 30 days prior to the Baseline Visit or is concurrently enrolled in any non-interventional research of any type judged to be scientifically or medically incompatible with the study as deemed by the Investigator in consultation with the Sponsor
Subject experienced an adverse reaction to study drug in the SPIMM-201 study that contraindicates further treatment with elamipretide in the opinion of the Investigator and/or Sponsor
Female subjects who are pregnant, planning to become pregnant, or lactating
Subject has undergone an in-patient hospitalization within the 1 month prior to the Screening Visit or is likely to need in-patient hospitalization or a surgical procedure during the course of the study
Subject has a creatinine clearance ≤30 mL/min as calculated by the Cockcroft Gault equation
Subject has a corrected QT interval (QTc) elongation defined as a QTc >450 msec in male subjects and >480msec in female subjects. Note: At the initial electrocardiogram (ECG), if QTc exceeds these parameters, the ECG may be repeated 2 more times, and the average of the 3 QTc values used to determine the subjects eligibility
Subject has uncontrolled hypertension in the judgment of the Investigator (e.g. elevated above >160 mmHg systolic or >100 mmHg diastolic despite appropriate treatment on two consecutive readings)
Subject has a history of clinically significant hypersensitivity or allergy to any of the excipients contained in the study drug
Subject has a history of active alcoholism or drug addiction during the year before the Screening Visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jim Carr
Organizational Affiliation
Stealth BioTherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of California
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Children's Hospital of Pittsburg of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
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