Mitochondrial MyopathiesPhase 3NuPowerNCT05162768
Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
A Phase 3 study testing Elamipretide in people with Mitochondrial Myopathies and Mitochondrial Pathology, run by Stealth BioTherapeutics Inc. at 32 sites in 10 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Mitochondrial Myopathies, Mitochondrial Pathology, Mitochondrial DNA Mutation
- What is being tested?
- Elamipretide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 32 sitesin 10 countries
- Study dates
- 29 Apr 2022to 4 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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:
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- POLG 1/2
- TWINKLE (C10ORF2)
- TYMP
- DGUOK
- TK2
- RRM2B
- RNASEH1
- SSBP
- MGME1
- DNA2
- ANT1 (SLC25A4)
- SUCLG1
- SUCLA2
- MPV17 or
- Other pathogenic mutations specific to nuclear DNA.
- 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:
- 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.
- 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).
- 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).
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
32 sites in 10 countries.
32 sites in 10 countries
United States9 sites
Akron Children's Hospital
Akron, Ohio, 44308
Rare Disease Research, LLC
Atlanta, Georgia, 30329
Massachusetts General Hospital
Boston, Massachusetts, 02114
UT Health,Center for the Treatment of Pediatric Neurodegenerative Disease
Houston, Texas, 77030
Columbia University Medical Center College of Physician and Surgeon
New York, New York, 10032
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh of UPMC Department of Genetics
Pittsburgh, Pennsylvania, 15224
University of California, San Diego
San Diego, California, 92093
Washington University School of Medicine
St Louis, Missouri, 63110
Italy6 sites
IRCCS Institute of Neorological Sciences of Bologna Bellaria Hospital
Bologna
University of Brescia, NeMO Clinical Center for Neuromuscular Diseases
Gussago, Brescia, 25064
Azienda Ospedaliero Universitaria Policlinico G. Martino
Messina, 98125
Istituto Nazionale Neurologico Carlo Besta
Milan, 20133
Azienda Ospedaliero Universitario Pisana, Dipartimento Ambientale di Neuroscienze
Pisa, 56126
Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore
Rome, Lazio, 00168
Spain4 sites
Hospital de la Sta Creu i Sant Pau
Barcelona, 8025
Hospital Clinic de Barcelona
Barcelona, 8036
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital la Fe de Valencia
Valencia, 46026
Germany3 sites
Universitaetsklinikum Carl Gustav Carus Dresden Neurologie
Dresden
Department of Neurology, University Clinics Munich
Munich, Bavaria, 80336
Univ of Tubingen, Hertie Institute for Clinical Brain Research
Tübingen
United Kingdom3 sites
University of Cambridge, Department of Clinical Neurosciences
Cambridge, CB2 0QQ
Queen Square Centre for Neuromuscular Diseases The National Hospital for Neurology and Neurosurgery
London, WC1N 3BG
Newcastle upon Tyne Hospitals Freeman Hospital
Newcastle, NE77DN
Australia2 sites
Calvary Health Care Bethlehem
Parkdale, Victoria, 3162
Royal North Shore Hospital Neurology
Sydney, New South Wales, 2065
Hungary2 sites
Semmelweis Egyetem Genomikai Medicina es Ritka Betegsegek
Budapest, 1083
University of Pécs, Department of Neurology Klinikai Kozpont - neurologiai Klinika
Pécs, 7624
New Zealand1 site
University of Auckland - Auckland City Hospital, Neurology Department
Auckland, 1023
About this study
Official title: A Phase 3 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Disease Resulting From Pathogenic Nuclear DNA Mutations (nPMD) NuPower
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).
Read the detailed 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.
- Conditions
- Mitochondrial Myopathies, Mitochondrial Pathology, Mitochondrial DNA Mutation, Mitochondrial Diseases, Mitochondrial DNA Deletion, Mitochondrial DNA Depletion
- Being tested
- Elamipretide, Placebo
- 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)
- Medical subject headings
- Mitochondrial Myopathies, Mitochondrial Diseases, Mitochondrial complex I deficiency, Muscle Weakness, Ophthalmoplegia, Chronic Progressive External
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElamipretideDrug
Also called MTP-131
60 mg of elamipretide administered as once daily 0.75 mL subcutaneous injections for 48 weeks
PlaceboDrug
Placebo administered as once daily 0.75 mL subcutaneous injections for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Elamipretide | Experimental | 0.75 mL of 80mg/mL solution of elamipretide for a single daily SC dose of 60mg elamipretide Receives: Drug: Elamipretide |
| Placebo | Placebo comparator | 0.75 mL of 80mg/mL solution of matching placebo for a single daily SC dose of 60mg Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-minute walk test (6MWT)
Change from Baseline in Distance Walked (in meters) on the Six-Minute Walk Test by Visit
Measured: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Secondary outcomes (3)
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
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.
Measured: Baseline, Weeks 12, 24, 36, 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2021
- Study start29 Apr 2022
- Primary completion30 Sep 2024
- Study completion4 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial MyopathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stealth BioTherapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05162768
- Sponsor's protocol ID
- SPIMD-301
- Acronym
- NuPower
- Status last verified
- Oct 2025
- First submitted
- 8 Dec 2021
- Last updated
- 24 Oct 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Disease Resulting From Pathogenic Nuclear DNA Mutations (nPMD) NuPower
- ClinicalTrials.gov ID
- NCT05162768
- Acronym / sponsor ID
- NuPower / SPIMD-301
- Conditions
- Mitochondrial Myopathies, Mitochondrial Pathology, Mitochondrial DNA Mutation, Mitochondrial Diseases, Mitochondrial DNA Deletion, Mitochondrial DNA Depletion
- Keywords
- primary mitochondrial myopathy (PMM), nuclear DNA mutations n(PMD), exercise intolerance, muscle weakness, mitochondrial dysfunction, POLG, TWINKLE, progressive external ophthalmoplegia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Stealth BioTherapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Apr 2022 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 4 Dec 2024 (actual)
- First posted
- 17 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Elamipretide | Experimental | Drug: Elamipretide0.75 mL of 80mg/mL solution of elamipretide for a single daily SC dose of 60mg elamipretide |
| Placebo | Placebo comparator | Drug: Placebo0.75 mL of 80mg/mL solution of matching placebo for a single daily SC dose of 60mg |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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:
- 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:
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElamipretideAlso: MTP-13160 mg of elamipretide administered as once daily 0.75 mL subcutaneous injections for 48 weeks | Drug | Elamipretide |
| PlaceboPlacebo administered as once daily 0.75 mL subcutaneous injections for 48 weeks | Drug | Placebo |
Primary outcome
Six-minute walk test (6MWT)
Time frame: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Change from Baseline in Distance Walked (in meters) on the Six-Minute Walk Test by Visit
3 secondary outcomes
5 times sit-to-stand test (5XSST)
Time frame: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Triple Timed up-and-go test (3TUG)
Time frame: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Patient Global Impression of Severity (PGI-S) Scale
Time frame: Baseline, Weeks 12, 24, 36, 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Elamipretide in people with Mitochondrial Myopathies and Mitochondrial Pathology, run by Stealth BioTherapeutics Inc. at 32 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Italy, Spain, Germany, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six-minute walk test (6MWT) (time frame: Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.