A Trial to Evaluate the Safety and Efficacy of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Extension

Overview

This is a multicenter phase 3 randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the safety and efficacy of daily subcutaneous injections of elamipretide in subjects with primary mitochondrial myopathy. This will be followed by an open-label treatment extension.

Full Title of Study: “A Phase 3 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Treatment Extension”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 20, 2019

Interventions

  • Combination Product: elamipretide
    • 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
  • Combination Product: placebo comparator
    • 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
  • Combination Product: elamipretide open label treatment
    • 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system

Arms, Groups and Cohorts

  • Experimental: Part 1: Elamipretide
    • Subjects will be randomized to receive either elamipretide or placebo for 24 weeks. For the elamipretide arm, subjects will administer daily 40 mg (0.5mL) subcutaneous injections of elamipretide.
  • Placebo Comparator: Part 1: Placebo
    • Subjects will be randomized to receive either elamipretide or placebo for 24 weeks. For the placebo arm, subjects will administer daily 40 mg (0.5 mL) subcutaneous injections of placebo for 24 weeks.
  • Experimental: Part 2: Elamipretide open label
    • Once subjects complete part 1, and meet continuation criteria, they will have the option to continue into an open-label treatment extension. Subjects will receive 40 mg (0.5 mL) subcutaneous injections of elamipretide for up to 144 weeks.

Clinical Trial Outcome Measures

Primary Measures

  • Change in distance walked on the six minute walk test (6MWT)
    • Time Frame: Baseline to 24 weeks
  • Change in total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
    • Time Frame: Baseline to 24 weeks
    • Each individual item score ranges from 1 (none) to 4 (severe). The total fatigue score ranges from 4-16. Lower values represent a better outcome. The total fatigue score is the sum of question 1 through question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.

Secondary Measures

  • Change in fatigue during activities score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA)
    • Time Frame: Baseline to 24 weeks
    • Each individual item score ranges from 1 (none) to 4 (severe). Lower values represent a better outcome. The total fatigue during activities score is the sum of question 2 and question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.
  • Change in the Neuro-QoL Fatigue Item Bank score
    • Time Frame: Baseline to 24 weeks
    • Each individual item score ranges from 1-5. Total raw score for the entire item bank ranges from 19-95. Raw scores will be calibrated using Item Response Theory Model. Lower values represent a better outcome. Individual items will be summed to calculate total scores.
  • Change in the most bothersome symptom score on the Primary Mitochondrial Myopathy Symptoms Assessment
    • Time Frame: Baseline to 24 weeks
    • The item score rangers from 1 (none) to 4 (severe). Lower values represent a better outcome. The most bothersome score is the average of the identified most bothersome symptom of the Primary Mitochondrial Myopathy Symptom Assessment by each subject.
  • Evaluate safety and tolerability through incidence of treatment emergent adverse events
    • Time Frame: Baseline to 28 weeks

Participating in This Clinical Trial

PART 1:

Inclusion Criteria

  • Willing and able to provide a signed informed consent form prior to participation in any trial-related procedures
  • Agrees to adhere to the trial requirements for the length of the trial, including the use of the elamipretide delivery system
  • Subject is ≥ 16 and ≤ 80 years of age
  • Diagnosed with PMM in the opinion of the investigator and confirmed by an Adjudication Committee
  • Woman of childbearing potential must agree to use a highly effective method of birth control

Exclusion Criteria

  • Subject has myopathic signs and or/symptoms due to a neuropathic process or gait problem that would interfere with the 6MWT, in the opinion of the Investigator
  • Female who are pregnant, planning to become pregnant, or breastfeeding/lactating
  • At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2
  • Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial.
  • Subject has clinically significant cardiac disease or prior interventional procedure and/or respiratory disease (medical history or current clinical findings) within 3 months of the Baseline Visit, in the opinion of the Investigator.
  • Subject has QTc elongation (using the correction factor utilized at the clinical site) defined as a QTc >450 msec in male subjects and >480 msec in female subjects.
  • ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following:

1. First degree AV-block

2. Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)

3. Right bundle branch block

  • Subject has severe vision impairment that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements
  • Subject has a seizure disorder that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements.
  • Active malignancy or any other cancer from which the subject has been disease-free for < 2 years.
  • Subject has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression, in the opinion of the Investigator.
  • Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
  • Subject has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000 cells x10^6/L at the Screening Visit.
  • Subject is currently participating or has participated in an interventional clinical trial (i.e.,investigational product or device, stem cell therapy, gene therapy) within 30 days of the Baseline Visit; or is currently enrolled in a non-interventional clinical trial (except for SPIMM-300) at the Baseline Visit which, in the opinion of the Investigator, may be potentially confounding with results of the current trial (e.g., exercise therapy trial).
  • Subject has previously received elamipretide (MTP-131), for any reason.
  • Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator.
  • 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 trial requirements.

PART 2:

Continuation Criteria:

  • Subjects must continue to be able and willing to adhere to the trial requirements.
  • Subject is appropriate to continue in Part 2 (i.e. subject was compliant in Part 1), in the opinion of the Investigator.
  • Subject has not had a serious adverse event (SAE)/serious adverse device effect (SADE) attributed to the elamipretide delivery system.
  • Subject has not permanently discontinued the elamipretide delivery system.

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Stealth BioTherapeutics Inc.
  • Provider of Information About this Clinical Study
    • Sponsor

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