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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days
University of California
San Diego, California, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Akron Children's Hospital
Akron, Ohio, United States
Children's Hospital of Pittsburg of UPMC
Pittsburgh, Pennsylvania, United States
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).
Time frame: Assessed at Baseline, Day 5 (end-of-treatment visit)
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
Change in Watts
Change in watts from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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.
Time frame: Days 1-5 and Day 7.
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5
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).
Time frame: Baseline, Day 5