- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02367014
Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (MMPOWER)
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 Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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San Diego, California, United States, 92093
- University of California
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Ohio
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Akron, Ohio, United States, 44308
- Akron Children's Hospital
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- Children's Hospital of Pittsburg of UPMC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Low Dose
elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days
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elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Other Names:
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Experimental: Intermediate dose
elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days
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elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Other Names:
|
Experimental: High dose
elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days
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elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
Other Names:
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Placebo Comparator: Placebo
In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.
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placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
Time Frame: Assessed at Baseline, Day 5 (end-of-treatment visit)
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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).
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Assessed at Baseline, Day 5 (end-of-treatment visit)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Maximum Oxygen Uptake (ml/kg/Min)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Ventilatory Efficiency (VE/VCO2 Slope)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Pre-exercise Lactate Levels (mg/dL)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Post-exercise Lactate Levels (mg/dL)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Respiratory Exchange Ratio (VCO2/VO2)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Respiratory Rate (Breaths/Min)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Ventilation (L/Min)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Heart Rate (Beats/Min)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Oxygen Saturation (% O2-saturated Hemoglobin)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Systolic Blood Pressure (mmHg)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Diastolic Blood Pressure (mmHg)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Peak Borg Dyspnea
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in VO2 Anaerobic Threshold (mL)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Watts
Time Frame: Baseline, Day 5
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Change in watts from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
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Baseline, Day 5
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Change in Temperature (°C)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in ECG-PR Interval (Msec)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in ECG-QRS Complex (Msec)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in ECG-QT Interval (Msec)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in ECG-QTc Interval (Msec)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Number of Participants Who Had Suicide Ideation, Suicidal Behavior, or Non-suicidal Self-injurious Behavior Post-screening.
Time Frame: Days 1-5 and Day 7.
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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.
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Days 1-5 and Day 7.
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Change in Creatine Phosphokinase (IU/L)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Alanine Aminotransferase (ALT) (U/L)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Aspartate Aminotransferase (AST) (U/L)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Change in Eosinophils (10^9 Cells/L)
Time Frame: Baseline, Day 5
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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).
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Baseline, Day 5
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPIMM-201
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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