A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly

NCT02245620 | Completed Phase 2 Results

• 1 other identifier: SPITM-201
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This was a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 41 elderly subjects with previous evidence of mitochondrial dysfunction to evaluate whether the administration of MTP-131 (elamipretide) will change either hand skeletal muscle energetics or muscle performance in age-related skeletal muscle mitochondrial dysfunction.

Conditions

Skeletal Muscle Mitochondrial Dysfunction in the Elderly

Keywords

Skeletal muscle dysfunction, MTP-131, Bendavia™; elamipretide

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)

  Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.

  From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

Secondary Outcomes (3)

• Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio

  From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

• Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)

  From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

• Mean Change From Baseline in Muscle Force-Time-Integral (FTI)

  From Baseline to Day 1 Hour 2, Day 3, and Day 7

Study Arms (2)

Elamipretide

EXPERIMENTAL

Elamipretide given as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.

Drug: Elamipretide

Placebo

PLACEBO COMPARATOR

Placebo (lyophilized excipients without elamipretide) given as an intravenous infusion at a rate of 60 mL/hr for 2 hours.

Drug: Placebo

Interventions

Elamipretide DRUG

Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours

Also known as: MTP-131, Bendavia™

Elamipretide

Placebo DRUG

Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours

Also known as: elamipretide

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are male and female adults aged ≥60 and ≤85 years
• Female subjects must be post-menopausal
• Have in vivo phosphorus-31 (31P) Magnetic Resonance Spectroscopy (MRS) and (Optical Spectra Scan (OPS) determined maximum adenosine triphosphate synthetic rate (ATPmax) \< 0.70 milliMol/second (mM/sec)
• Have in vivo 31P MRS and OPS determined P/O (Phosphate/Oxygen ratio) \< 1.9
• Are ambulatory and able to perform activities of daily living without assistance
• Had sufficient venous access for study drug administration and clinical testing.
• Could speak and read English fluently.
• Provided informed consent.

You may not qualify if:

• Had significant disease(s) or condition(s) which, in the opinion of the Investigator, may have put the subject at risk because of their participation in the study or may have influenced either the results of the study or the subject's ability to participate in the study.
• Had a history of rhabdomyolysis.
• Had been hospitalized within 3 months prior to Screening for major atherosclerotic events (e.g., myocardial infarction, target-vessel revascularization, coronary bypass surgery or stroke) or other major medical condition (as deemed by the Primary Investigator).
• Had any metal implants that could not be removed from the body that in the opinion of the Investigator were a contra-indication for undergoing the MRS procedure or any other protocol-related procedure.
• Had an implanted cardiac pacemaker or other implanted cardiac device.
• Had a serum sodium level \<136 milliequivalents per litre (mEq/L) at Screening or Pre-infusion.
• Had a hemoglobin level \<12 g/dL at Screening or Pre-infusion.
• Had chronic, uncontrolled hypertension as judged by the Investigator (e.g., Baseline systolic blood pressure \[SBP\] \>140 mm Hg, diastolic blood pressure \[DBP\] \> 90 mm Hg) or a SBP \>150 mm Hg or DBP \>95 mm Hg at the time of Screening or Baseline (if the initial blood pressure \[BP\] reading was above these values, the reading may have been repeated one time within 20 minutes of the initial reading).
• Had a body mass index (BMI) of \<16 or \>35 kg/m2.
• Had a creatinine clearance \<45 mL/min as calculated by the Cockcroft Gault equation.
• Had a 12-lead electrocardiogram (ECG) demonstrating severe bradycardia (heart rate \< 40 bpm) or average corrected QC interval (QTc) \>450 ms for males and \> 470 ms for females, and in the opinion of the Investigator was clinically significant. (If on the initial ECG, QTc exceeded 450 ms for males or 470 ms for females, the ECG was to be repeated 2 more times and the average of the 3 QTc values was to be used to determine the subject's eligibility).
• Had a neurologic disorder that in the opinion of the Investigator was a contra-indication for enrollment into the study.
• Had any symptoms consistent with or a current diagnosis of peripheral neuropathy, such as numbness, tingling, pain, or altered sensation of hands or feet.
• Had an active, systemic autoimmune disease other than autoimmune thyroid disease (e.g., diabetes, lupus, rheumatoid arthritis) that currently required treatment or was likely to require treatment during the study.
• Subject's right hand had a history of mobility impairment, fractures, arthritis, hand surgery, muscle disease or other injury that may interfere with any study procedure.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (1)

The University of Washington Medical Center

Seattle, Washington, 98104, United States

Location

MeSH Terms

Interventions

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

Results Point of Contact

• Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc

jim.carr@stealthbt.com

1-617-600-6888

Study Officials

• Jim Carr

  Stealth BioTherapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: September 17, 2014
• First Posted: September 19, 2014
• Study Start: January 15, 2015
• Primary Completion: July 6, 2016
• Study Completion: July 6, 2016
• Last Updated: June 23, 2020
• Results First Posted: June 23, 2020

Record last verified: 2020-06

Locations

US (1)