Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy

NCT ID: NCT02367014

Last Updated: 2019-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2016-04-30

Brief Summary

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.

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).

Conditions

Mitochondrial Myopathy

Keywords

Mitochondrial Myopathy; Primary Mitochondrial Disease; Bendavia™; elamipretide

Study Design

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

Study Groups

Low Dose

elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days

Group Type: EXPERIMENTAL

elamipretide (low dose)

Intervention Type: DRUG

elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

Intermediate dose

elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days

Group Type: EXPERIMENTAL

elamipretide (intermediate dose)

Intervention Type: DRUG

elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

High dose

elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days

Group Type: EXPERIMENTAL

elamipretide (high dose)

Intervention Type: DRUG

elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

Placebo

In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days

Interventions

elamipretide (low dose)

elamipretide (0.01 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

Intervention Type: DRUG

elamipretide (intermediate dose)

elamipretide (0.10 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

Intervention Type: DRUG

elamipretide (high dose)

elamipretide (0.25 mg/kg/hr) administered as single day intravenous infusion over 2 hours for 5 days

Intervention Type: DRUG

Placebo

placebo (at each dose cohort) administered as single day intravenous infusion over 2 hours for 5 days

Intervention Type: DRUG

Other Intervention Names

MTP-131; MTP-131; MTP-131

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

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

Other Identifiers

SPIMM-201

Identifier Type: -

Identifier Source: org_study_id