A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension
Condition: Primary Mitochondrial Myopathy
MeSH terms: Muscular Diseases; Mitochondrial Myopathies
Intervention: elamipretide; placebo comparator; elamipretide open label treatment
Intervention description: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system; 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system; 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 218.0
Sex: All
Minimum age: 16 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Myopathy; PMD; Primary Mitochondrial Disease; MTP-131; elamipretide

Summary:

      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.
    

Eligibility criteria:

        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 6 minute walk test (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 Atrioventricular bock (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.