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

NCT03323749 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: SPIMM-301
• Study Type: interventional
• Target: 218
• Locations: 7 countries
• Sites: 27

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.

Conditions

Primary Mitochondrial Myopathy

Keywords

Myopathy; PMD; Primary Mitochondrial Disease; MTP-131; elamipretide

Outcome Measures

Primary Outcomes (2)

• Six-minute Walk Test (6MWT)

  Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit

  Baseline to 24 weeks

• Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)

  Change from Baseline in Total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) by visit. 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.

  Baseline to 24 weeks

Secondary Outcomes (4)

• Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).

  Baseline to 24 weeks

• Neuro-QoL Fatigue Activities of Daily Living

  Baseline to 24 weeks

• Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment

  Baseline to 24 weeks

• Neuro-QoL Fatigue Short Form Score

  24 Weeks

Study Arms (3)

Part 1: Elamipretide

EXPERIMENTAL

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

Combination Product: elamipretide

Part 1: Placebo

PLACEBO COMPARATOR

Placebo SC daily

Combination Product: placebo comparator

Part 2: Elamipretide open label

EXPERIMENTAL

Elamepretide 40 mg (0.5 mL) SC daily

Combination Product: elamipretide open label treatment

Interventions

elamipretide COMBINATION_PRODUCT

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

Also known as: MTP-131

Part 1: Elamipretide

placebo comparator COMBINATION_PRODUCT

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

Also known as: Placebo

Part 1: Placebo

elamipretide open label treatment 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

Part 2: Elamipretide open label

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• First degree Atrioventricular bock (AV-block)
• Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
• 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.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (27)

University of California San Diego

La Jolla, California, 92093, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cleveland Clinical Neurological Institute

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Adult Metabolic Diseases Clinic

Vancouver, British Colombia, Canada

Location

McMaster University Medical Center

Hamilton, Ontario, Canada

Location

Copenhagen Neuromuscular Center

Copenhagen, DK-2100, Denmark

Location

University Hospital of Bonn

Bonn, 53105, Germany

Location

Klinikum der Universität München, Friedrich-Baur Institute

Munich, 80336, Germany

Location

Institute of Genomic Medicine and Rare Disorders

Budapest, 1083, Hungary

Location

IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital

Bologna, 40139, Italy

Location

Azienda Ospedaliero Universitaria Policlinico G. Martino

Messina, 98125, Italy

Location

Istituto Nazionale Neurologico Carlo Besta

Milan, 20133, Italy

Location

Dipartimento Ambientale di Neuroscienze

Pisa, 56126, Italy

Location

Ospedale Pediatrico Bambin Gesù

Rome, 00165, Italy

Location

Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli

Rome, 00168, Italy

Location

MRC Centre for Neuromuscular Diseases

London, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39574155 DERIVED

• 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.

  PMID: 37268435 DERIVED

MeSH Terms

Conditions

Muscular Diseases

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Results Point of Contact

• Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc

jim.carr@stealthbt.com

1-617-600-6888

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: October 27, 2017
• Study Start: October 9, 2017
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: January 24, 2022
• Results First Posted: April 2, 2021

Record last verified: 2022-01

Locations

DE (2); DK (1); CA (2); IT (6); HU (1); GB (2); US (13)