Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)

NCT05162768 | Completed Phase 3 FDA Drug

• 1 other identifier: SPIMD-301
• Study Type: interventional
• Target: 102
• Locations: 10 countries
• Sites: 32

Brief Summary

SPIMD-301 is a 48-week, randomized, double-blind, parallel-group, placebo-controlled trial to assess efficacy and safety of single daily subcutaneous (SC) administration of elamipretide as a treatment for subjects with primary mitochondrial myopathy associated with nuclear DNA mutations (nPMD).

Conditions

Mitochondrial Myopathies; Mitochondrial Pathology; Mitochondrial DNA Mutation; Mitochondrial Diseases; Mitochondrial DNA Deletion; Mitochondrial DNA Depletion; Mitochondrial Metabolism Defect; Mitochondrial Complex I Deficiency

Keywords

primary mitochondrial myopathy (PMM); nuclear DNA mutations n(PMD); exercise intolerance; muscle weakness; mitochondrial dysfunction; POLG; TWINKLE; progressive external ophthalmoplegia; Elamipretide; mitochondrial replisome; replisome related mutations; MTP-131; primary mitochondrial disease (PMD)

Outcome Measures

Primary Outcomes (1)

• Six-minute walk test (6MWT)

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

  Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)

Secondary Outcomes (3)

• 5 times sit-to-stand test (5XSST)

  Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)

• Triple Timed up-and-go test (3TUG)

  Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)

• Patient Global Impression of Severity (PGI-S) Scale

  Baseline, Weeks 12, 24, 36, 48

Study Arms (2)

Elamipretide

EXPERIMENTAL

0.75 mL of 80mg/mL solution of elamipretide for a single daily SC dose of 60mg elamipretide

Drug: Elamipretide

Placebo

PLACEBO COMPARATOR

0.75 mL of 80mg/mL solution of matching placebo for a single daily SC dose of 60mg

Drug: Placebo

Interventions

Elamipretide DRUG

60 mg of elamipretide administered as once daily 0.75 mL subcutaneous injections for 48 weeks

Also known as: MTP-131

Elamipretide

Placebo DRUG

Placebo administered as once daily 0.75 mL subcutaneous injections for 48 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide a signed informed consent form (ICF) prior to participation in any trial-related procedures.
• Agrees and is able to adhere to the trial requirements for the length of the trial, including administration of assigned treatment.
• Is ≥18 years and ≤ 70 years of age at the time of screening.
• Diagnosed with nPMD with a predominant clinical manifestation of myopathy, which must include progressive external ophthalmoplegia (PEO) and exercise intolerance and/or skeletal muscle weakness, with genetic confirmation of either:
• Nuclear DNA mutation of the mitochondrial replisome (replisome-related mutations), which include the following genes:
• POLG 1/2
• TWINKLE (C10ORF2)
• TYMP
• DGUOK
• TK2
• RRM2B
• RNASEH1
• SSBP
• MGME1
• DNA2

You may not qualify if:

• Is unable to perform the 6MWT, 3TUG, or 5XSST functional tests. The use of a gait assist device is allowed; however, use should remain consistent for the entire duration of the trial.
• Female subjects who are pregnant, planning to become pregnant, or breastfeeding/lactating.
• Walks \< 150 meters or \> 450 meters during the 6MWT (Screening Visit only).
• The estimated glomerular filtration rate (eGFR) is \< 30 mL/min/1.73 m2, using the Modification of Diet in Renal Disease (MDRD) Study equation (Screening Visit only).
• Has undergone an in-patient hospitalization within 30 days prior to screening or has a planned hospitalization or a surgical procedure during the trial, unless, in the opinion of the Investigator, it is concluded that it will not impact the outcome measurements of the trial.
• Has clinically significant respiratory disease and/or cardiac disease that would interfere with trial assessments, in the opinion of the Investigator.
• Has had any prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to screening.
• Has history of or current severe neurologic impairment, severe epilepsy, severe ataxia, or severe neuropathy that may interfere with their ability to complete all trial requirements, in the opinion of the Investigator.
• Active malignancy or any other cancer from which the subject has been disease-free for \< 2 years. Localized squamous or non-invasive basal cell skin carcinomas are allowed, if appropriately treated prior to screening.
• Has had a solid organ transplant.
• Has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
• Has a history of a systemic eosinophilic illness and/or an eosinophil count \>1,000 cells x106/L at the Screening Visit.
• 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 prior to current trial; or is currently enrolled in a non-interventional clinical trial that, in the opinion of the Investigator, may be potentially confounding to the results of the current trial (e.g., exercise therapy trial).
• Has received elamipretide (MTP-131) within the past one year of the Screening Visit.
• Has a history of active substance abuse during the year prior, in the opinion of the Investigator.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (32)

University of California, San Diego

San Diego, California, 92093, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30329, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center College of Physician and Surgeon

New York, New York, 10032, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh of UPMC Department of Genetics

Pittsburgh, Pennsylvania, 15224, United States

Location

UT Health,Center for the Treatment of Pediatric Neurodegenerative Disease

Houston, Texas, 77030, United States

Location

Royal North Shore Hospital Neurology

Sydney, New South Wales, 2065, Australia

Location

Calvary Health Care Bethlehem

Parkdale, Victoria, 3162, Australia

Location

Department of Neurology, University Clinics Munich

Munich, Bavaria, 80336, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden Neurologie

Dresden, Germany

Location

Univ of Tubingen, Hertie Institute for Clinical Brain Research

Tübingen, Germany

Location

Semmelweis Egyetem Genomikai Medicina es Ritka Betegsegek

Budapest, 1083, Hungary

Location

University of Pécs, Department of Neurology Klinikai Kozpont - neurologiai Klinika

Pécs, 7624, Hungary

Location

University of Brescia, NeMO Clinical Center for Neuromuscular Diseases

Gussago, Brescia, 25064, Italy

Location

Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore

Rome, Lazio, 00168, Italy

Location

IRCCS Institute of Neorological Sciences of Bologna Bellaria Hospital

Bologna, Italy

Location

Azienda Ospedaliero Universitaria Policlinico G. Martino

Messina, 98125, Italy

Location

Istituto Nazionale Neurologico Carlo Besta

Milan, 20133, Italy

Location

Azienda Ospedaliero Universitario Pisana, Dipartimento Ambientale di Neuroscienze

Pisa, 56126, Italy

Location

Radboud University Medical Center

Nijmegen, 6525, Netherlands

Location

University of Auckland - Auckland City Hospital, Neurology Department

Auckland, 1023, New Zealand

Location

Helse Bergen HF

Bergen, 5021, Norway

Location

Hospital de la Sta Creu i Sant Pau

Barcelona, 8025, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital la Fe de Valencia

Valencia, 46026, Spain

Location

University of Cambridge, Department of Clinical Neurosciences

Cambridge, CB2 0QQ, United Kingdom

Location

Queen Square Centre for Neuromuscular Diseases The National Hospital for Neurology and Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Newcastle upon Tyne Hospitals Freeman Hospital

Newcastle, NE77DN, United Kingdom

Location

MeSH Terms

Conditions

Mitochondrial Myopathies; Mitochondrial Diseases; Mitochondrial complex I deficiency; Muscle Weakness; Ophthalmoplegia, Chronic Progressive External

Interventions

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

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Eye Diseases; Chronic Disease; Disease Attributes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Trial personnel and subjects will be blinded to treatment until the database is locked. The Investigator will contact the Sponsor prior to unblinding any subject's treatment sequence unless in the instance of a medical emergency.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this 48-week trial, subjects will be randomized (in a ratio of 1:1) to one of two groups: single daily subcutaneous doses of 60mg elamipretide, or, matching placebo, using a central randomization stratified by whether or not subjects have nPMD associated with replisome-related mutations. 130 subjects, consisting of 90 subjects with nPMD associated mutations of the mitochondrial replisome for primary analysis and an additional subset of up to 40 subjects who have nPMD associated with other non-replisome-related pathogenic mutations specific to nuclear DNA. Three periods: Screening (up to 28 days), Treatment (48 Weeks) and Follow-Up Period (4 weeks).

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 17, 2021
• Study Start: April 29, 2022
• Primary Completion: September 30, 2024
• Study Completion: December 4, 2024
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); AU (2); GB (3); NO (1); DE (3); HU (2); IT (6); ES (4); NZ (1); NL (1)