A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension

NCT ID: NCT03323749

Last Updated: 2022-01-24

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

218 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-09

Study Completion Date

2020-02-10

Brief Summary

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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

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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.

Conditions

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Primary Mitochondrial Myopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Part 1: Elamipretide

40 mg (0.5mL) elamipretide subcutaneous (SC) daily

Group Type EXPERIMENTAL

elamipretide

Intervention Type COMBINATION_PRODUCT

40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system

Part 1: Placebo

Placebo SC daily

Group Type PLACEBO_COMPARATOR

placebo comparator

Intervention Type COMBINATION_PRODUCT

40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system

Part 2: Elamipretide open label

Elamepretide 40 mg (0.5 mL) SC daily

Group Type EXPERIMENTAL

elamipretide open label treatment

Intervention Type COMBINATION_PRODUCT

40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system

Interventions

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elamipretide

40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system

Intervention Type 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

Intervention Type 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

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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MTP-131 Placebo

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California San Diego

La Jolla, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Rare Disease Research, LLC

Atlanta, Georgia, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cleveland Clinical Neurological Institute

Cleveland, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Texas Health Science Center

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Adult Metabolic Diseases Clinic

Vancouver, British Colombia, Canada

Site Status

McMaster University Medical Center

Hamilton, Ontario, Canada

Site Status

Copenhagen Neuromuscular Center

Copenhagen, , Denmark

Site Status

University Hospital of Bonn

Bonn, , Germany

Site Status

Klinikum der Universität München, Friedrich-Baur Institute

Munich, , Germany

Site Status

Institute of Genomic Medicine and Rare Disorders

Budapest, , Hungary

Site Status

IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital

Bologna, , Italy

Site Status

Azienda Ospedaliero Universitaria Policlinico G. Martino

Messina, , Italy

Site Status

Istituto Nazionale Neurologico Carlo Besta

Milan, , Italy

Site Status

Dipartimento Ambientale di Neuroscienze

Pisa, , Italy

Site Status

Ospedale Pediatrico Bambin Gesù

Rome, , Italy

Site Status

Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli

Rome, , Italy

Site Status

MRC Centre for Neuromuscular Diseases

London, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Canada Denmark Germany Hungary Italy United Kingdom

References

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Karaa A, Bertini E, Carelli V, Cohen B, Ennes GM, Falk MJ, Goldstein A, Gorman G, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Abbruscato A, Brown DA, Sullivan A, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators. Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial. Orphanet J Rare Dis. 2024 Nov 21;19(1):431. doi: 10.1186/s13023-024-03421-5.

Reference Type DERIVED
PMID: 39574155 (View on PubMed)

Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023 Jul 18;101(3):e238-e252. doi: 10.1212/WNL.0000000000207402. Epub 2023 Jun 2.

Reference Type DERIVED
PMID: 37268435 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SPIMM-301

Identifier Type: -

Identifier Source: org_study_id

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