Clinical trial NCT03323749: A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension
Official title: A Phase 3 Randomized, 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: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary Mitochondrial Myopathy
Keywords: Myopathy
PMD
Primary Mitochondrial Disease
MTP-131
elamipretide
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-27
Enrollment: 218
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Part 11 is a 24-week, randomized, double-blind, parallel-group, placebo-controlled assessment of the efficacy and safety of single daily subcutaneous (SC) doses of 40 mg elamipretide (vs placebo) administered with the elamipretide delivery system as a treatment for subjects with primary mitochondrial myopathy (PMM). Part 2 was to assess the long-term safety and tolerability of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for up to 144 weeks.

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.

Primary outcomes:
measure: Six-minute Walk Test (6MWT)
timeFrame: Baseline to 24 weeks
measure: Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).
timeFrame: Baseline to 24 weeks
measure: Neuro-QoL Fatigue Activities of Daily Living
timeFrame: Baseline to 24 weeks
measure: Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment
timeFrame: Baseline to 24 weeks
measure: Neuro-QoL Fatigue Short Form Score
timeFrame: 24 Weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinical Neurological Institute
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine/Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Vancouver
country: Canada
facility: Adult Metabolic Diseases Clinic
state: British Colombia
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Copenhagen
country: Denmark
facility: Copenhagen Neuromuscular Center
city: Bonn
country: Germany
facility: University Hospital of Bonn
city: Munich
country: Germany
facility: Klinikum der Universität München, Friedrich-Baur Institute
city: Budapest
country: Hungary
facility: Institute of Genomic Medicine and Rare Disorders
city: Bologna
country: Italy
facility: IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital
city: Messina
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G. Martino
city: Milan
country: Italy
facility: Istituto Nazionale Neurologico Carlo Besta
city: Pisa
country: Italy
facility: Dipartimento Ambientale di Neuroscienze
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambin Gesù
city: Rome
country: Italy
facility: Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli
city: London
country: United Kingdom
facility: MRC Centre for Neuromuscular Diseases
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
References: