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

Primary Purpose

Mitochondrial Myopathies, Mitochondrial Pathology, Mitochondrial DNA Mutation

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Elamipretide
Placebo
Sponsored by
Stealth BioTherapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mitochondrial Myopathies focused on measuring 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)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California, San Diego
  • Children's Hospital Colorado
  • Rare Disease Research, LLC
  • Johns Hopkins University Department of Genetic Medicine
  • Massachusetts General Hospital
  • Washington University School of Medicine
  • Columbia University Medical Center College of Physician and Surgeon
  • Akron Children's Hospital
  • The Children's Hospital of Philadelphia
  • University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh of UPMC Department of Genetics
  • UT Health,Center for the Treatment of Pediatric Neurodegenerative Disease
  • Royal North Shore Hospital Neurology
  • Calvary Health Care Bethlehem
  • Department of Neurology, University Clinics Munich
  • Universitaetsklinikum Carl Gustav Carus Dresden Neurologie
  • Univ of Tubingen, Hertie Institute for Clinical Brain Research
  • Semmelweis Egyetem Genomikai Medicina es Ritka Betegsegek
  • University of Pécs, Department of Neurology Klinikai Kozpont - neurologiai Klinika
  • University of Brescia, NeMO Clinical Center for Neuromuscular Diseases
  • Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore
  • IRCCS Institute of Neorological Sciences of Bologna Bellaria Hospital
  • Azienda Ospedaliero Universitaria Policlinico G. Martino
  • Istituto Nazionale Neurologico Carlo Besta
  • Azienda Ospedaliero Universitario Pisana, Dipartimento Ambientale di Neuroscienze
  • Radboud University Medical Center
  • University of Auckland - Auckland City Hospital, Neurology Department
  • Helse Bergen HF
  • Hospital de la Sta Creu i Sant Pau
  • Hospital Clinic de Barcelona
  • Hospital Universitario 12 de Octubre
  • Hospital la Fe de Valencia
  • University of Cambridge, Department of Clinical Neurosciences
  • Queen Square Centre for Neuromuscular Diseases The National Hospital for Neurology and Neurosurgery
  • Newcastle upon Tyne Hospitals Freeman Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Elamipretide

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Six-minute walk test (6MWT)
Change from Baseline in Distance Walked (in meters) on the Six-Minute Walk Test by Visit

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
December 8, 2021
Last Updated
October 11, 2023
Sponsor
Stealth BioTherapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05162768
Brief Title
Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
Acronym
NuPower
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 29, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stealth BioTherapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Elamipretide
Arm Type
Experimental
Arm Description
0.75 mL of 80mg/mL solution of elamipretide for a single daily SC dose of 60mg elamipretide
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.75 mL of 80mg/mL solution of matching placebo for a single daily SC dose of 60mg
Intervention Type
Drug
Intervention Name(s)
Elamipretide
Other Intervention Name(s)
MTP-131
Intervention Description
60 mg of elamipretide administered as once daily 0.75 mL subcutaneous injections for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo administered as once daily 0.75 mL subcutaneous injections for 48 weeks
Primary Outcome Measure Information:
Title
Six-minute walk test (6MWT)
Description
Change from Baseline in Distance Walked (in meters) on the Six-Minute Walk Test by Visit
Time Frame
Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Secondary Outcome Measure Information:
Title
5 times sit-to-stand test (5XSST)
Description
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.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Title
Triple Timed up-and-go test (3TUG)
Description
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.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 52 (End of Trial Visit)
Title
Patient Global Impression of Severity (PGI-S) Scale
Description
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.
Time Frame
Baseline, Weeks 12, 24, 36, 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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 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. Exclusion Criteria: 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.
Facility Information:
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rare Disease Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Johns Hopkins University Department of Genetic Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center College of Physician and Surgeon
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh of UPMC Department of Genetics
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
UT Health,Center for the Treatment of Pediatric Neurodegenerative Disease
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Royal North Shore Hospital Neurology
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Calvary Health Care Bethlehem
City
Parkdale
State/Province
Victoria
ZIP/Postal Code
3162
Country
Australia
Facility Name
Department of Neurology, University Clinics Munich
City
Munich
State/Province
Bavaria
ZIP/Postal Code
80336
Country
Germany
Facility Name
Universitaetsklinikum Carl Gustav Carus Dresden Neurologie
City
Dresden
Country
Germany
Facility Name
Univ of Tubingen, Hertie Institute for Clinical Brain Research
City
Tübingen
Country
Germany
Facility Name
Semmelweis Egyetem Genomikai Medicina es Ritka Betegsegek
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
University of Pécs, Department of Neurology Klinikai Kozpont - neurologiai Klinika
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
University of Brescia, NeMO Clinical Center for Neuromuscular Diseases
City
Gussago
State/Province
Brescia
ZIP/Postal Code
25064
Country
Italy
Facility Name
Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Facility Name
IRCCS Institute of Neorological Sciences of Bologna Bellaria Hospital
City
Bologna
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Policlinico G. Martino
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Istituto Nazionale Neurologico Carlo Besta
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Azienda Ospedaliero Universitario Pisana, Dipartimento Ambientale di Neuroscienze
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Radboud University Medical Center
City
Nijmegen
ZIP/Postal Code
6525
Country
Netherlands
Facility Name
University of Auckland - Auckland City Hospital, Neurology Department
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Helse Bergen HF
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Hospital de la Sta Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
8025
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital la Fe de Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
University of Cambridge, Department of Clinical Neurosciences
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Queen Square Centre for Neuromuscular Diseases The National Hospital for Neurology and Neurosurgery
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
Facility Name
Newcastle upon Tyne Hospitals Freeman Hospital
City
Newcastle
ZIP/Postal Code
NE77DN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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

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