Back to resultsSafety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (MMPOWER)
Primary Purpose
Mitochondrial Myopathy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
elamipretide (low dose)
elamipretide (intermediate dose)
elamipretide (high dose)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mitochondrial Myopathy focused on measuring Mitochondrial Myopathy, Primary Mitochondrial Disease, Bendavia™, elamipretide
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of mitochondrial disease believed to impair the mitochondrial respiratory chain.
- Eligibility requires prior genetic confirmation of mitochondrial disease.
- Diagnosis of mitochondrial myopathy judged by the Investigators to be due to existing mitochondrial disease.
- Must be able to complete a Screening Visit 6MWT.
- Body mass index (BMI) score >15.0 and <35.0 kg/m2 at Screening Visit.
- Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the ICF until two months after the last dose of study drug.
Exclusion Criteria:
- 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.
- Had any exclusionary Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores at Screening Visit.
- Hospitalized (admitted as in-patient) within 1 month prior to the Baseline Visit.
- A history of type 1 diabetes mellitus (T1DM).
- Uncontrolled Type 1 (T1DM) or Type 2 diabetes mellitus (T2DM), in the opinion of the investigator.
- A creatinine clearance <45 mL/min as calculated by the Cockcroft Gault equation.
- Requires pacemaker, defibrillator, or has undergone cardiac surgery within 2 years of Screening Visit.
- QTc elongation defined as a QTc >450 msec in male subjects and >480 msec in female subjects.
- Uncontrolled hypertension (>160 mmHg systolic or >100 mmHg diastolic) at Screening Visit.
- History of rhabdomyolysis defined as an acute rise in the serum creatine phosphokinase (CPK) value that, in the opinion of the investigator, caused clinically significant symptoms.
- Serum sodium more than 5 meq/L below the reference lower limit of normal at Screening Visit.
Participated in another interventional clinical trial within 3 months of the screening visit or is currently enrolled in a non-interventional clinical trial judged by the Investigator to be incompatible with the current trial.
- Other protocol-defined inclusion/exclusion criteria may apply.
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 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Low Dose
Intermediate dose
High dose
Placebo
Arm Description
elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days
elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days
elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days
In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.
Outcomes
Primary Outcome Measures
Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
Change in distance walked as measured by meters on the 6-minute walk test from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Secondary Outcome Measures
Change in Maximum Oxygen Uptake (ml/kg/Min)
Change in maximum oxygen uptake as measured by mL/kg/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Ventilatory Efficiency (VE/VCO2 Slope)
Change in ventilatory efficiency as measured by the VE/VCO2 slope from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)
Change in aerobic efficiency as measured by ΔO2 consumption/Δ work ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)
Change in oxygen utilization as measured by ΔVO2/ΔlogVE ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)
Change in oxygen uptake kinetics (mean response time) as measured by seconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Pre-exercise Lactate Levels (mg/dL)
Change in pre-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Post-exercise Lactate Levels (mg/dL)
Change in post-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Respiratory Exchange Ratio (VCO2/VO2)
Change in peak respiratory exchange ratio as measured by VCO2/VO2 from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Respiratory Rate (Breaths/Min)
Change in peak respiratory rate as measured by breaths/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Ventilation (L/Min)
Change in peak ventilation as measured by L/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Heart Rate (Beats/Min)
Change in peak heart rate as measured by beats per minute from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Oxygen Saturation (% O2-saturated Hemoglobin)
Change in peak oxygen saturation as measured by percentage of O2-saturated hemoglobin from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Systolic Blood Pressure (mmHg)
Change in peak systolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Diastolic Blood Pressure (mmHg)
Change in peak diastolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Peak Borg Dyspnea
Change in peak Borg dyspnea as measured by 0-10 with 0 meaning no breathlessness and 10 meaning maximal breathlessness from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in VO2 Anaerobic Threshold (mL)
Change in VO2 anaerobic threshold as measured by mL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Watts
Change in watts from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Temperature (°C)
Change in temperature as measured by units of Celsius from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in ECG-PR Interval (Msec)
Change in PR interval as measured by ECG in milliseconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in ECG-QRS Complex (Msec)
Change in QRS complex as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in ECG-QT Interval (Msec)
Change in QT interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in ECG-QTc Interval (Msec)
Change in QTc interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Number of Participants Who Had Suicide Ideation, Suicidal Behavior, or Non-suicidal Self-injurious Behavior Post-screening.
Number of participants with suicide ideation, suicidal behavior, or non-suicidal self-injurious behavior post-screening as measured on Days 1-5, and Day 7 on the Columbia Suicide Severity Rating Scale (CSSRS). A yes/no binary response is utilized in the following ten categories: 1 - Wish to be Dead; 2 - Non-specific Active Suicidal Thoughts; 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5 - Active Suicidal Ideation with Specific Plan and Intent; 6 - Preparatory Acts or Behavior; 7 - Aborted Attempt; 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); 10 - Completed Suicide. A yes/no binary response is also utilized in assessing self-injurious behavior without suicidal intent. A lower score means a better outcome whereas a higher score means a worse outcome.
Change in Creatine Phosphokinase (IU/L)
Change in Creatine Phosphokinase as measured by IU/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Alanine Aminotransferase (ALT) (U/L)
Change in Alanine aminotransferase (ALT) as measured by (U/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Aspartate Aminotransferase (AST) (U/L)
Change in aspartate aminotransferase (AST) as measured by U/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Change in Eosinophils (10^9 Cells/L)
Change in eosinophils as measured by (10^9 cells/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Full Information
NCT ID
NCT02367014
First Posted
February 9, 2015
Last Updated
December 8, 2019
Sponsor
Stealth BioTherapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02367014
Brief Title
Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy
Acronym
MMPOWER
Official Title
Phase 1/2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Clinical Study for the Safety, Tolerability, and Efficacy of IV MTP-131 for Mitochondrial Myopathy in Genetically Confirmed Mitochondrial Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stealth BioTherapeutics Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase 1/2, multi-center, randomized, double-blind, multiple ascending dose, placebo-controlled study that enrolled 36 subjects with mitochondrial myopathy associated with genetically confirmed mitochondrial disease to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MTP-131 in this patient population.
Detailed Description
This multi-center, randomized, double-blind, placebo-controlled study enrolled 36 subjects into 3 cohorts of 12 subjects each to evaluate treatment with 3 ascending doses of intravenous elamipretide (0.01, 0.10, and 0.25 mg/kg/hr infused for 2 hours). After each cohort, a Safety Monitoring Board (SMB) determined if dose escalation to the next higher dose of elamipretide was warranted. Each cohort went through 3 distinct periods: Screening, Treatment, and Follow-up.
The Screening Period started with informed consent and may have lasted up to 40 days. During this period, screening procedures to determine subject eligibility for the study occurred, including confirmation of disease, which incorporated a committee review of the investigator-submitted diagnosis and genetic results. The Treatment Period began on Day 1 (Visit 2) and lasted for 5 days (until Day 5 [Visit 6]). Within each cohort, 9 subjects were randomized to active drug and 3 subjects were randomized to placebo on Day 1 and subjects received treatment once a day for 5 consecutive days. Safety, tolerability, and efficacy measures were performed at pre-specified times. The Follow-up Period began at the time of discharge on Day 5. Subjects returned to the study center for the Follow-up Visit on Day 7 (+1 day).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Myopathy
Keywords
Mitochondrial Myopathy, Primary Mitochondrial Disease, Bendavia™, elamipretide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose
Arm Type
Experimental
Arm Description
elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days
Arm Title
Intermediate dose
Arm Type
Experimental
Arm Description
elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days
Arm Title
High dose
Arm Type
Experimental
Arm Description
elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.
Intervention Type
Drug
Intervention Name(s)
elamipretide (low dose)
Other Intervention Name(s)
MTP-131
Intervention Description
elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Intervention Type
Drug
Intervention Name(s)
elamipretide (intermediate dose)
Other Intervention Name(s)
MTP-131
Intervention Description
elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Intervention Type
Drug
Intervention Name(s)
elamipretide (high dose)
Other Intervention Name(s)
MTP-131
Intervention Description
elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
Primary Outcome Measure Information:
Title
Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
Description
Change in distance walked as measured by meters on the 6-minute walk test from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Assessed at Baseline, Day 5 (end-of-treatment visit)
Secondary Outcome Measure Information:
Title
Change in Maximum Oxygen Uptake (ml/kg/Min)
Description
Change in maximum oxygen uptake as measured by mL/kg/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Ventilatory Efficiency (VE/VCO2 Slope)
Description
Change in ventilatory efficiency as measured by the VE/VCO2 slope from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)
Description
Change in aerobic efficiency as measured by ΔO2 consumption/Δ work ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)
Description
Change in oxygen utilization as measured by ΔVO2/ΔlogVE ratio from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)
Description
Change in oxygen uptake kinetics (mean response time) as measured by seconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Pre-exercise Lactate Levels (mg/dL)
Description
Change in pre-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Post-exercise Lactate Levels (mg/dL)
Description
Change in post-exercise lactate levels as measured by mg/dL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Respiratory Exchange Ratio (VCO2/VO2)
Description
Change in peak respiratory exchange ratio as measured by VCO2/VO2 from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Respiratory Rate (Breaths/Min)
Description
Change in peak respiratory rate as measured by breaths/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Ventilation (L/Min)
Description
Change in peak ventilation as measured by L/min from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Heart Rate (Beats/Min)
Description
Change in peak heart rate as measured by beats per minute from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Oxygen Saturation (% O2-saturated Hemoglobin)
Description
Change in peak oxygen saturation as measured by percentage of O2-saturated hemoglobin from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Systolic Blood Pressure (mmHg)
Description
Change in peak systolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Diastolic Blood Pressure (mmHg)
Description
Change in peak diastolic blood pressure as measured by mmHg from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Peak Borg Dyspnea
Description
Change in peak Borg dyspnea as measured by 0-10 with 0 meaning no breathlessness and 10 meaning maximal breathlessness from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in VO2 Anaerobic Threshold (mL)
Description
Change in VO2 anaerobic threshold as measured by mL from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Watts
Description
Change in watts from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Temperature (°C)
Description
Change in temperature as measured by units of Celsius from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in ECG-PR Interval (Msec)
Description
Change in PR interval as measured by ECG in milliseconds from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in ECG-QRS Complex (Msec)
Description
Change in QRS complex as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in ECG-QT Interval (Msec)
Description
Change in QT interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in ECG-QTc Interval (Msec)
Description
Change in QTc interval as measured by ECG in msec from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Number of Participants Who Had Suicide Ideation, Suicidal Behavior, or Non-suicidal Self-injurious Behavior Post-screening.
Description
Number of participants with suicide ideation, suicidal behavior, or non-suicidal self-injurious behavior post-screening as measured on Days 1-5, and Day 7 on the Columbia Suicide Severity Rating Scale (CSSRS). A yes/no binary response is utilized in the following ten categories: 1 - Wish to be Dead; 2 - Non-specific Active Suicidal Thoughts; 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5 - Active Suicidal Ideation with Specific Plan and Intent; 6 - Preparatory Acts or Behavior; 7 - Aborted Attempt; 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); 10 - Completed Suicide. A yes/no binary response is also utilized in assessing self-injurious behavior without suicidal intent. A lower score means a better outcome whereas a higher score means a worse outcome.
Time Frame
Days 1-5 and Day 7.
Title
Change in Creatine Phosphokinase (IU/L)
Description
Change in Creatine Phosphokinase as measured by IU/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Alanine Aminotransferase (ALT) (U/L)
Description
Change in Alanine aminotransferase (ALT) as measured by (U/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Aspartate Aminotransferase (AST) (U/L)
Description
Change in aspartate aminotransferase (AST) as measured by U/L from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
Title
Change in Eosinophils (10^9 Cells/L)
Description
Change in eosinophils as measured by (10^9 cells/L) from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time Frame
Baseline, Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of mitochondrial disease believed to impair the mitochondrial respiratory chain.
Eligibility requires prior genetic confirmation of mitochondrial disease.
Diagnosis of mitochondrial myopathy judged by the Investigators to be due to existing mitochondrial disease.
Must be able to complete a Screening Visit 6MWT.
Body mass index (BMI) score >15.0 and <35.0 kg/m2 at Screening Visit.
Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the ICF until two months after the last dose of study drug.
Exclusion Criteria:
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.
Had any exclusionary Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores at Screening Visit.
Hospitalized (admitted as in-patient) within 1 month prior to the Baseline Visit.
A history of type 1 diabetes mellitus (T1DM).
Uncontrolled Type 1 (T1DM) or Type 2 diabetes mellitus (T2DM), in the opinion of the investigator.
A creatinine clearance <45 mL/min as calculated by the Cockcroft Gault equation.
Requires pacemaker, defibrillator, or has undergone cardiac surgery within 2 years of Screening Visit.
QTc elongation defined as a QTc >450 msec in male subjects and >480 msec in female subjects.
Uncontrolled hypertension (>160 mmHg systolic or >100 mmHg diastolic) at Screening Visit.
History of rhabdomyolysis defined as an acute rise in the serum creatine phosphokinase (CPK) value that, in the opinion of the investigator, caused clinically significant symptoms.
Serum sodium more than 5 meq/L below the reference lower limit of normal at Screening Visit.
Participated in another interventional clinical trial within 3 months of the screening visit or is currently enrolled in a non-interventional clinical trial judged by the Investigator to be incompatible with the current trial.
Other protocol-defined inclusion/exclusion criteria may apply.
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
15213
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy
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