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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05162768
Other study ID # SPIMD-301
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date April 29, 2022
Est. completion date October 2024

Study information

Verified date December 2023
Source Stealth BioTherapeutics Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Description:

This 48-week randomized, double-blind, parallel-group, placebo-controlled trial will enroll approximately 130 subjects, consisting of 90 subjects who have nPMD associated with pathogenic mutations of the mitochondrial replisome("replisome-related mutations") 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 the nuclear DNA. Efficacy and safety of single daily SC doses of elamipretide administered as a treatment for subjects who have primary mitochondrial myopathy associated with nPMD will be determined. Subjects will be randomized 1:1 to 60mg Elamipretide or matching placebo groups.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 102
Est. completion date October 2024
Est. primary completion date September 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: A subject must meet all of the following inclusion criteria at the Screening and Baseline Visit (unless otherwise specified) to be eligible for inclusion in the SPIMD-301 trial: 1. Willing and able to provide a signed informed consent form (ICF) prior to participation in any trial-related procedures. 2. Agrees and is able to adhere to the trial requirements for the length of the trial, including administration of assigned treatment. 3. Is =18 years and = 70 years of age at the time of screening. 4. 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: 1. 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 - ANT1 (SLC25A4) - SUCLG1 - SUCLA2 - MPV17 or 2. Other pathogenic mutations specific to nuclear DNA. 5. Women of childbearing potential must agree to use one of the following methods of birth control from the date they sign the ICF until 28 days after the last dose of IMP: 1. Abstinence, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use a highly effective method of contraception should they become sexually active. 2. Relationships with male partners who have been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit). 3. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system. Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit). 6. Male subjects with female partners of childbearing potential must be willing to use a highly effective method of contraception from the date they sign the ICF until 28 days after the last dose of IMP. Exclusion Criteria: 1. 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. 2. Female subjects who are pregnant, planning to become pregnant, or breastfeeding/lactating. 3. Walks < 150 meters or > 450 meters during the 6MWT (Screening Visit only). 4. 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). 5. 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. 6. Has clinically significant respiratory disease and/or cardiac disease that would interfere with trial assessments, in the opinion of the Investigator. 7. Has had any prior interventional cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within 3 months prior to screening. 8. 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. 9. 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. 10. Has had a solid organ transplant. 11. Has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 12. Has a history of a systemic eosinophilic illness and/or an eosinophil count >1,000 cells x106/L at the Screening Visit. 13. 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). 14. Has received elamipretide (MTP-131) within the past one year of the Screening Visit. 15. Has a history of active substance abuse during the year prior, in the opinion of the Investigator.

Study Design


Intervention

Drug:
Elamipretide
60 mg of elamipretide administered as once daily 0.75 mL subcutaneous injections for 48 weeks
Placebo
Placebo administered as once daily 0.75 mL subcutaneous injections for 48 weeks

Locations

Country Name City State
Australia Calvary Health Care Bethlehem Parkdale Victoria
Australia Royal North Shore Hospital Neurology Sydney New South Wales
Germany Universitaetsklinikum Carl Gustav Carus Dresden Neurologie Dresden
Germany Department of Neurology, University Clinics Munich Munich Bavaria
Germany Univ of Tubingen, Hertie Institute for Clinical Brain Research Tübingen
Hungary Semmelweis Egyetem Genomikai Medicina es Ritka Betegsegek Budapest
Hungary University of Pécs, Department of Neurology Klinikai Kozpont - neurologiai Klinika Pecs
Italy IRCCS Institute of Neorological Sciences of Bologna Bellaria Hospital Bologna
Italy University of Brescia, NeMO Clinical Center for Neuromuscular Diseases Gussago Brescia
Italy Azienda Ospedaliero Universitaria Policlinico G. Martino Messina
Italy Istituto Nazionale Neurologico Carlo Besta Milano
Italy Azienda Ospedaliero Universitario Pisana, Dipartimento Ambientale di Neuroscienze Pisa
Italy Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore Roma Lazio
Netherlands Radboud University Medical Center Nijmegen
New Zealand University of Auckland - Auckland City Hospital, Neurology Department Auckland
Norway Helse Bergen HF Bergen
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital de la Sta Creu i Sant Pau Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital la Fe de Valencia Valencia
United Kingdom University of Cambridge, Department of Clinical Neurosciences Cambridge
United Kingdom Queen Square Centre for Neuromuscular Diseases The National Hospital for Neurology and Neurosurgery London
United Kingdom Newcastle upon Tyne Hospitals Freeman Hospital Newcastle
United States Akron Children's Hospital Akron Ohio
United States Rare Disease Research, LLC Atlanta Georgia
United States Massachusetts General Hospital Boston Massachusetts
United States UT Health,Center for the Treatment of Pediatric Neurodegenerative Disease Houston Texas
United States Columbia University Medical Center College of Physician and Surgeon New York New York
United States The Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh of UPMC Department of Genetics Pittsburgh Pennsylvania
United States Washington University School of Medicine Saint Louis Missouri
United States University of California, San Diego San Diego California

Sponsors (1)

Lead Sponsor Collaborator
Stealth BioTherapeutics Inc.

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Hungary,  Italy,  Netherlands,  New Zealand,  Norway,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 5 times sit-to-stand test (5XSST) Change from Baseline in Total time (in seconds) to complete the 5XSST. Participant is directed to stand up straight as quickly as possible 5 times, without stopping in between, keeping arms folded across the chest. An average time is calculated. Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Secondary Triple Timed up-and-go test (3TUG) Change from Baseline in Total time (in seconds) to complete the 3TUG. Participant is directed to stand up from chair, walk at normal pace to the line on the floor 3 meters away, turn, walk back to the chair at normal pace, sit down again; activity is timed, in seconds. Activity is repeated 3 times consecutively without rest and an average time is calculated. Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Secondary Patient Global Impression of Severity (PGI-S) Scale Change from Baseline for PGI of Severity (PGI-S) Scale. Patient-reported current health status by week and at end of treatment. PGI-S Scale is a categorical scale and asks the participant to "rate the severity of your muscle weakness symptoms today" as one of the following categories: None, Mild, Moderate, Severe, or Very Severe. None means better health status, and best outcome, Very severe means worse health status and worse outcome. Baseline, Weeks 12, 24, 36, 48
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