Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study

Stealth BioTherapeutics Inc.30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Primary Mitochondrial Disease

Interventions

ElamipretideDRUG

4 weeks of treatment with 40 mg elamipretide administered once daily subcutaneously

PlaceboDRUG

4 weeks of treatment with placebo administered once daily subcutaneously

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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

Locations (4)

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

Outcomes

Primary Outcomes

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.

Time frame: End of Week 4 and End of Week 12

Secondary Outcomes

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.

Time frame: Last 7 days prior to the date of end of treatment visit

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

Data from ClinicalTrials.gov

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