An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)

An Open-label, Multi-centre Study to Evaluate the Long-term Safety and Tolerability of REN001 in Subjects With Primary Mitochondrial Myopathy (PMM)

Status

Terminated

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05267574

Enrollment

155

Registered

2022-03-04

Start date

2022-02-01

Completion date

2024-01-31

Last updated

2024-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Mitochondrial Myopathy

Brief summary

This study is designed to evaluate the long-term safety and tolerability of REN001 administered once daily to subjects with PMM due to mitochondrial DNA mutations (mtDNA-PMM) or nuclear DNA mutations (nDNA-PMM). Subjects with mtDNA mutations will have previously completed Study REN001-201 or participated in Study REN001-101. Subjects with nDNA mutations who enroll in this study will be REN001- naïve.

Detailed description

This study is designed to evaluate the long-term safety and tolerability of REN001 administered once daily to subjects with PMM due to mitochondrial DNA mutations (mtDNA=PMM) or nuclear DNA mutations (nDNA-PMM). Subjects with mtDNA mutations will have previously completed Study REN001-201 (which is referred to as the STRIDE study) or participated in Study REN001-101. Subjects with nDNA mutations who enroll in this study will be REN001- naïve. Eligible subjects will be treated with REN001 100mg orally, once daily for 24 months. Following the baseline visit there are planned visits at at defined time points. A final follow-up telephone call will be made by the study centre to the subject approximately 30 days after the last dose of study drug.

Interventions

DRUGREN001

Once daily dosing

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* mtDNA-PMM subjects: Completed treatment in STRIDE or was participating in Study REN001-101 when the study stopped due to the COVID-19 pandemic, and in the opinion of the Investigator and Sponsor had been compliant with the study requirements OR nDNA-PMM subjects: Subjects aged 18 years or older with known nuclear (nDNA) pathogenic variants with a major muscle phenotype consisting of objective myopathy with poor exercise tolerance. Proof of pathogenicity must be provided. Must be able to walk at least 100m in the screening 12MWT and the limitations in walk test must be primarily due to the energy deficit and not due to ataxia or any other condition. For subjects under 25 years old only: confirmation of bone growth plate closure by wrist radiograph. * Have PMM which continues to be primarily characterized by exercise intolerance or active muscle pain. * Willing and able to swallow the REN001 gelatin capsules. * Concomitant medications (including supplements) intended for the treatment of PMM or other co-morbidities likely to remain stable throughout participation in the study where clinically possible. * Signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. * Females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception from baseline through to approximately 30 days after the last dose of study drug. Males with partners who are women of childbearing potential (WOCBP) must also use contraception from baseline through to 14 weeks after the last dose of study drug.

Exclusion criteria

* Anticipated to need a peroxisome proliferator-activated receptor (PPAR) agonist other than REN001 during the study. * Intent to donate blood, or blood components during the study or within one month after completion of the study. * Current drug dependency. Use of opiates/cannabis for medical reasons is acceptable with prescription evidence or at the Investigator's discretion. * Current alcohol dependency. * Any medical, psychiatric or laboratory condition that may increase the risk associated with study participation or interfere with the interpretation of study results and, in the judgment of the Investigator and Medical Monitor, would make the subject inappropriate for entry into this study. * Pregnant or nursing female Subjects with mtDNA mutations can enroll at STRIDE Week 24 visit, STRIDE-FU visit, after exiting from STRIDE or after exiting REN001-101 (UK only). Subjects enrolling after exiting from either of the 2 feeder mtDNA studies and all subjects with nDNA mutations will be required to fulfill additional

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Baseline through study termination, an average of 12.1 months	Number of participants with AEs and severity

Secondary

Measure	Time frame	Description
Change in Distance Walked During a 12 Minute Walk Test	Baseline to Month 24	Distance walked in meters
Change in Modified Fatigue Impact Scale (MFIS) Score	Baseline to Month 24	The MFIS is a 21-item scale to describe the impact of fatigue on physical, cognitive, and psychosocial functioning. The questionnaire includes 9 physical, 10 cognitive, and 2 psychosocial items with each item scored between 0=Never and 4=Almost Always
Change in Patient Global Impression of Severity (PGIS) Score	Baseline to Month 24	The PGIS is a 2-item questionnaire to describe the severity of fatigue and muscle symptoms. Each item is scored as Absent, Mild, Moderate, Severe, or Very Severe
Change in Brief Pain Inventory (BPI) Score	Baseline to Month 24	The BPI is a 15-item questionnaire to describe severity of pain and its interference on functioning. The questionnaire includes 4 pain severity items each scored between 0=No Pain and 10= Pain, and 7 pain interference items each scored between 0=Does not Interfere and 10=Completely Interferes
Absolute Values, Changes From Baseline, and Incidence of Potentially Clinically Significant Changes in Laboratory Safety Tests, Electrocardiograms, Supine Vital Signs, and Eye Assessments	Study Termination	Number of participants
Change in 36-Item Short Form Health Survey (SF-36) Score	Baseline to Month 24	The SF-36 is a 36-item questionnaire to describe health status and quality of life. The questionnaire includes 8 domains (physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions). Items are scored, summed into domains, and transformed into a scale of 0-100
Change Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score	Baseline to Month 24	The WPAI:SHP is a 6-item questionnaire to describe impairment in work and activities due to a certain disease. Items are scored, summed, and transformed into a scale of 0-100%
Change in Patient Global Impression of Change (PGIC) Score	Baseline to Month 24	The PGIC is a 2-item questionnaire to describe the change in fatigue and muscle symptoms since starting the study. Each item is scored as Very Much Worse, Moderately Worse, Minimally Worse, No Change, Minimally Improved, Moderately Improved, or Very Much Improved
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Short Form - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 13a Scores	Baseline to Month 24	The PROMIS Short Form - FACIT Fatigue 13a is a 13-item questionnaire to describe fatigue and its impact upon daily activities and function. Each item is scored between 1=Not At All and 5=Very Much

Countries

Australia, Belgium, Canada, Denmark, France, Germany, Hungary, Italy, Netherlands, New Zealand, Spain, United Kingdom

Participant flow

Participants by arm

Arm	Count
REN001 100 mg once daily REN001: Once daily dosing	155
Total	155

Baseline characteristics

Characteristic	REN001
Age, Customized 18-25 years	7 Participants
Age, Customized 26-45 years	53 Participants
Age, Customized 46-64 years	78 Participants
Age, Customized >= 65 years	17 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	148 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants
Race/Ethnicity, Customized Asian	4 Participants
Race/Ethnicity, Customized Not Reported	5 Participants
Race/Ethnicity, Customized Other	2 Participants
Race/Ethnicity, Customized White	144 Participants
Region of Enrollment Australia	17 participants
Region of Enrollment Europe	133 participants
Region of Enrollment North America	5 participants
Sex: Female, Male Female	103 Participants
Sex: Female, Male Male	52 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 155
other Total, other adverse events	123 / 155
serious Total, serious adverse events	12 / 155

Outcome results

Primary

Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs

Number of participants with AEs and severity

Time frame: Baseline through study termination, an average of 12.1 months

Arm	Measure	Group	Value (NUMBER)
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Total TESAEs	12 participants
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Mild TEAEs	68 participants
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Moderate TEAEs	50 participants
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Severe TEAEs	5 participants
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	TEAEs leading to study drug discontinuation	1 participants
REN001	Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs	Total TEAEs	123 participants

Secondary

Absolute Values, Changes From Baseline, and Incidence of Potentially Clinically Significant Changes in Laboratory Safety Tests, Electrocardiograms, Supine Vital Signs, and Eye Assessments

Number of participants

Time frame: Study Termination

Secondary

Change in 36-Item Short Form Health Survey (SF-36) Score

The SF-36 is a 36-item questionnaire to describe health status and quality of life. The questionnaire includes 8 domains (physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions). Items are scored, summed into domains, and transformed into a scale of 0-100