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

NCT02367014 | Completed Phase 1 Results DMC

• 1 other identifier: SPIMM-201
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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.

Conditions

Mitochondrial Myopathy

Keywords

Mitochondrial Myopathy; Primary Mitochondrial Disease; Bendavia™; elamipretide

Outcome Measures

Primary Outcomes (1)

• 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).

  Assessed at Baseline, Day 5 (end-of-treatment visit)

Secondary Outcomes (27)

• Change in Maximum Oxygen Uptake (ml/kg/Min)

  Baseline, Day 5

• Change in Ventilatory Efficiency (VE/VCO2 Slope)

  Baseline, Day 5

• Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)

  Baseline, Day 5

• Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)

  Baseline, Day 5

• Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)

  Baseline, Day 5

Study Arms (4)

Low Dose

EXPERIMENTAL

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

Drug: elamipretide (low dose)

Intermediate dose

EXPERIMENTAL

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

Drug: elamipretide (intermediate dose)

High dose

EXPERIMENTAL

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

Drug: elamipretide (high dose)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

elamipretide (low dose) DRUG

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

Also known as: MTP-131

Low Dose

elamipretide (intermediate dose) DRUG

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

Also known as: MTP-131

Intermediate dose

elamipretide (high dose) DRUG

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

Also known as: MTP-131

High dose

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (4)

University of California

San Diego, California, 92093, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Children's Hospital of Pittsburg of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Mitochondrial Myopathies

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

CPET was not performed on all subjects.Sensitivity analysis on change from Baseline in pre-and post-exercise lactate levels was not completed.Data from study sites were combined for efficacy and safety analyses.No site- effect analysis was performed.

Results Point of Contact

• Title: Jim Carr PharmD Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics Inc.

jim.carr@stealthbt.com

617-600-6888

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: February 20, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 27, 2019
• Results First Posted: December 27, 2019

Record last verified: 2019-12

Locations

US (4)