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

NCT ID: NCT02805790

Last Updated: 2020-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-22
• Study Completion Date: 2017-03-23

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.

Conditions

Primary Mitochondrial Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Elamipretide, Then Placebo

Participants first received 40 mg of elamipretide once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received placebo administered once daily subcutaneously for 4 weeks.

Group Type: EXPERIMENTAL

Elamipretide

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

4 weeks of treatment with placebo administered once daily subcutaneously

Placebo, Then Elamipretide

Participants first received placebo once daily subcutaneously for 4 weeks. After a washout period of 4 weeks, they then received 40 mg of elamipretide once daily subcutaneously for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Elamipretide

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

4 weeks of treatment with placebo administered once daily subcutaneously

Interventions

Elamipretide

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

Intervention Type: DRUG

Placebo

4 weeks of treatment with placebo administered once daily subcutaneously

Intervention Type: DRUG

Other Intervention Names

Bendavia; MTP-131

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Carr

Role: STUDY_DIRECTOR

Stealth BioTherapeutics

Locations

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

Countries

United States

References

Gwaltney C, Stokes J, Aiudi A, Mazar I, Ollis S, Love E, Karaa A, Houts CR, Wirth RJ, Shields AL. Psychometric performance of the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) in a randomized, double-blind, placebo-controlled crossover study in subjects with mitochondrial disease. J Patient Rep Outcomes. 2022 Dec 23;6(1):129. doi: 10.1186/s41687-022-00534-y.

Reference Type: DERIVED

PMID: 36562873 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SPIMM-202

Identifier Type: -

Identifier Source: org_study_id