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

Mitochondrial Diseases Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05162768
• Other study ID #: SPIMD-301
• Status: Active, not recruiting
• Phase: Phase 3
• 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
• 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.

Related Conditions & MeSH terms

• Mitochondrial Diseases
• Mitochondrial DNA Depletion
• Mitochondrial Myopathies
• Mitochondrial Pathology
• Muscular Diseases

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