Clinical trial NCT02805790: Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Mitochondrial Disease
Keywords: Primary Mitochondrial Disease
Mitochondrial Myopathy
Elamipretide
MTP-131
Bendavia™
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-06-20
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Distance Walked on the 6-minute Walk Test (6MWT) by Visit
timeFrame: End of Week 4 and End of Week 12
Secondary outcomes:
measure: Wrist Accelerometer Counts by Day
timeFrame: Last 7 days prior to the date of end of treatment visit
measure: Average Hip Accelerator Counts by Day
timeFrame: Last 7 days prior to the date of end of treatment visit
measure: Neuro-QoL Fatigue Short Form Score: Total T-Scores (Question 1-8)
timeFrame: End of Week 4 and End of Week 12
measure: Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score by Week
timeFrame: Last 7 days of Week 4 and Last 7 days of Week 12
measure: Triple Timed Up and Go (3TUG) Test by Visit
timeFrame: End of Week 4 and End of Week 12
measure: Patient Global Assessment [PGA] Score by Visit, Continuous
timeFrame: End of Week 4 and End of Week 12
measure: Patient Global Assessment by Visit, Categorical
timeFrame: End of Week 4 and End of Week 12
measure: Physician Global Assessment (PhGA) By Visit, Continuous
timeFrame: End of Week 4 and End of Week 12
measure: Physician Global Assessment (PhGA) By Visit, Categorical
timeFrame: End of Week 4 and End of Week 12
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburg of UPMC
state: Pennsylvania
Study officials:
affiliation: Stealth BioTherapeutics
name: Jim Carr
role: STUDY_DIRECTOR
References: