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A Trial to Evaluate the Safety and Efficacy of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Extension (MMPOWER-3)

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ClinicalTrials.gov Identifier: NCT03323749
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Primary Mitochondrial Myopathy Combination Product: elamipretide Combination Product: placebo comparator Combination Product: elamipretide open label treatment Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 27, 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Muscle Disorders

Arm Intervention/treatment
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.
Combination Product: elamipretide
40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system
Other Name: MTP-131

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.
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
Other Name: Placebo

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.
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




Primary Outcome Measures :
  1. Change in distance walked on the six minute walk test (6MWT) [ Time Frame: Baseline to 24 weeks ]
  2. 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 Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Evaluate safety and tolerability through incidence of treatment emergent adverse events [ Time Frame: Baseline to 28 weeks ]

Other Outcome Measures:
  1. Part 2: Evaluate the long term safety and tolerability of elamipretide using the elamipretide delivery system through incidence of treatment emergent adverse events [ Time Frame: Starting at week 24 up to 144 weeks ]


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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03323749


Locations
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Lilly Lee    619-543-2816    lil083@ucsd.edu   
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Thu Quan    650-736-8166    tquan@stanford.edu   
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Michelle Hite    720-777-4690    michelle.hite@childrenscolorado.org   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Erica Kelly    617-724-7726    elkelly@mgh.harvard.edu   
United States, New York
Columbia University Medical Center Enrolling by invitation
New York, New York, United States, 10032
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Contact: Hilary Tonni, BSN, MSE, RN, CCRC    330-543-4743    htonni@chcmca.org   
Cleveland Clinical Neurological Institute Recruiting
Cleveland, Ohio, United States, 44195
Contact: Irys Caristo    216-444-0173    caristi@ccf.org   
United States, Pennsylvania
Children's Hospital of Philadelphia Enrolling by invitation
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Michele Graham    412-692-3476    michele.graham@chp.edu   
United States, Texas
Baylor College of Medicine/Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: May Ali    832-822-1630    maali@bcm.edu   
University of Texas Health Science Center Recruiting
Houston, Texas, United States, 77030
Contact: Stephanie Maldonado    713-500-5372    Stephanie.Maldonado@uth.tmc.edu   
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Laurie Guidry    206-987-0058    laurie.guidry@seattlechildrens.org   
Canada, British Colombia
Adult Metabolic Diseases Clinic Recruiting
Vancouver, British Colombia, Canada
Contact: Anna Koochin    604-875-4111 ext 21423    anna.koochin@vch.ca   
Denmark
Copenhagen Neuromuscular Center Recruiting
Copenhagen, Denmark, DK-2100
Contact: Jane Dorte Pedersen    45-35455667    jane.dorte.pedersen.01@regionh.dk   
Hungary
Institute of Genomic Medicine and Rare Disorders Recruiting
Budapest, Hungary, 1083
Contact: Gyorgyi Bathori    36206632514    molnarmj@gmail.com   
United Kingdom
Royal Victoria Infirmary Recruiting
Newcastle Upon Tyne, United Kingdom
Contact: Alexandra Bright    441912088565    alexandra.bright@nuth.nhs.uk   
Sponsors and Collaborators
Stealth BioTherapeutics Inc.

Responsible Party: Stealth BioTherapeutics Inc.
ClinicalTrials.gov Identifier: NCT03323749     History of Changes
Other Study ID Numbers: SPIMM-301
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stealth BioTherapeutics Inc.:
Myopathy
PMD
Primary Mitochondrial Disease
MTP-131
elamipretide

Additional relevant MeSH terms:
Muscular Diseases
Mitochondrial Myopathies
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Mitochondrial Diseases
Metabolic Diseases