Primary Mitochondrial MyopathyPhase 2/3NCT05267574
An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)
A Phase 2/3 study testing REN001 in people with Primary Mitochondrial Myopathy, run by Reneo Pharma Ltd at 29 sites in 12 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Mitochondrial Myopathy
- What is being tested?
- REN001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 29 sitesin 12 countries
- Study dates
- 1 Feb 2022to 31 Jan 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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 exclusion criteria during their additional screening visit. This is required for the mtDNA-PMM subjects due to the gap in study drug treatment and period of time without study assessments. The additional exclusion criteria are:
- Clinically significant kidney disease or impairment calculated as eGFR Grade 2 or above <60ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation at Screening.
- Clinically significant liver disease or impairment of AST or ALT Grade 2 or above (>2.5 x ULN), or Total bilirubin > 1.6 x ULN or >ULN with other signs and symptoms of hepatotoxicity at Screening.
- Subjects with uncontrolled diabetes and/or a Screening HbA1c of ≥11%.
- Evidence of significant concomitant clinical disease that may need a change in management during the study or could interfere with the conduct or safety of this study. (Stable well-controlled chronic conditions such hypercholesterolemia, gastroesophageal reflux, or depression under control with medication (other than tricyclic antidepressants), are acceptable provided the symptoms and medications would not be predicted to compromise safety or interfere with the tests and interpretations of this study.)
- Subjects with a history of cancer. A history of in situ basal cell carcinoma in the skin is allowed.
- Clinically significant cardiac disease and/or clinically significant ECG abnormalities such as 2nd degree heart block, symptomatic tachyarrhythmia or unstable arrhythmia (right bundle branch block, left fascicular block and long PR interval are not excluded) that in the opinion of the Investigator should exclude the subject from completing exercise tests.
Trial locations and contacts
29 sites in 12 countries.
29 sites in 12 countries
France6 sites
Centre de Référence des Maladies Neuromusculaires
Angers, 49933
Hôpital Neurologique
Bron, 69599
Hôpital Roger Salengro
Lille, Hauts-de-France, 59037
Nice Teaching Hospital
Nice
Hôpitaux Universitaires Pitié Salpêtrière
Paris, 75013
CHU de Strasbourg- Hopital de Hautepierre
Strasbourg, 6700
Italy5 sites
IRCCS Institute of Neurological Sciences of Bologna
Bologna, 40139
A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari
Messina, Sicily, 98125
Istituto Nazionale Neurologico Carlo Besta
Milan, 20100
U.O. di Neurologia - Neurofisiopatologia
Pisa, 56100
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit
Rome, Lazio, 00168
Australia3 sites
PARC Clinical Research
Adelaide, South Australia, 5000
The Alfred Hospital
Melbourne, Victoria, 3004
Royal North Shore Hospital
St Leonards, New South Wales, 2065
United Kingdom3 sites
Queen Square Centre for Neuromuscular Diseases
London, Greater London, WC1N 3BG
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
Salford Royal NHS Foundation Trust
Salford, M5 5AP
Canada2 sites
M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)
Calgary, Alberta, T2E 7Z4
Vancouver General Hospital
Vancouver, V5Z 1M9
Germany2 sites
University Hospital Bonn Clinic and Polyclinic for Neurology
Bonn, 53127
Medical Center of the University of Munich Friedrich Baur Institute at the Neurological Clinic and Polyclinic
Munich, 80336
Hungary2 sites
Semmelweis University Insitute of Genomics and Rare Disorders
Budapest, 1082
University of Pécs Clinical Centre
Pécs, 7624
Spain2 sites
Hospital Universitario 12 de Octubre
Madrid, 20841
Hospital Universitari i Politècnic La Fe
Valencia, 46026
New Zealand1 site
Centre for Brain Research Neurogenetic Clinic
Grafton, Auckland, 1042
About this study
Official title: An Open-label, Multi-centre Study to Evaluate the Long-term Safety and Tolerability of REN001 in Subjects With Primary Mitochondrial Myopathy (PMM)
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.
Read the 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.
- Conditions
- Primary Mitochondrial Myopathy
- Being tested
- REN001
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REN001Drug
Once daily dosing
| Study group | Role | What they receive |
|---|---|---|
| REN001 | Experimental | 100 mg once daily Receives: Drug: REN001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline through study termination, an average of 12.1 months
Secondary outcomes (9)
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
Measured: Study Termination
Change in Distance Walked During a 12 Minute Walk Test
Distance walked in meters
Measured: Baseline to Month 24
Change in Modified Fatigue Impact Scale (MFIS) Score
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
Measured: Baseline to Month 24
Change in Patient Global Impression of Severity (PGIS) Score
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
Measured: Baseline to Month 24
Change in Brief Pain Inventory (BPI) Score
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
Measured: Baseline to Month 24
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Short Form - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 13a Scores
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
Measured: Baseline to Month 24
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
Measured: Baseline to Month 24
Change Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score
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%
Measured: Baseline to Month 24
Change in Patient Global Impression of Change (PGIC) Score
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
Measured: Baseline to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2022
- Study start1 Feb 2022
- Primary completion14 Dec 2023
- Study completion31 Jan 2024
Why it stopped: Parent study failed to show therapeutic effect
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Mitochondrial MyopathyStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reneo Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Grainne Gorman, MD, Principal investigator, Newcastle Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05267574
- Sponsor's protocol ID
- REN001-202
- Status last verified
- Apr 2024
- First submitted
- 24 Feb 2022
- Last updated
- 28 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-centre Study to Evaluate the Long-term Safety and Tolerability of REN001 in Subjects With Primary Mitochondrial Myopathy (PMM)
- ClinicalTrials.gov ID
- NCT05267574
- Acronym / sponsor ID
- REN001-202
- Conditions
- Primary Mitochondrial Myopathy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Parent study failed to show therapeutic effect
- Enrolment
- 155 participants (actual)
- Lead sponsor
- Reneo Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 14 Dec 2023 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 4 Mar 2022 (actual)
- Results
- Posted 28 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| REN001 | Experimental | Drug: REN001100 mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
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 |
|---|---|---|
| REN001Once daily dosing | Drug | REN001 |
Primary outcome
Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs
Time frame: Baseline through study termination, an average of 12.1 months
Number of participants with AEs and severity
9 secondary outcomes
Absolute Values, Changes From Baseline, and Incidence of Potentially Clinically Significant Changes in Laboratory Safety Tests, Electrocardiograms, Supine Vital Signs, and Eye Assessments
Time frame: Study Termination
Change in Distance Walked During a 12 Minute Walk Test
Time frame: Baseline to Month 24
Change in Modified Fatigue Impact Scale (MFIS) Score
Time frame: Baseline to Month 24
Change in Patient Global Impression of Severity (PGIS) Score
Time frame: Baseline to Month 24
Change in Brief Pain Inventory (BPI) Score
Time frame: Baseline to Month 24
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Short Form - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 13a Scores
Time frame: Baseline to Month 24
Change in 36-Item Short Form Health Survey (SF-36) Score
Time frame: Baseline to Month 24
Change Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score
Time frame: Baseline to Month 24
Change in Patient Global Impression of Change (PGIC) Score
Time frame: Baseline to Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Grainne Gorman, MD principal investigator
Newcastle Hospital NHS Foundation Trust
29 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing REN001 in people with Primary Mitochondrial Myopathy, run by Reneo Pharma Ltd at 29 sites in 12 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 6 inclusion and 13 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: stopped early, as of the sponsor's last update on 28 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in France, Italy, Australia, United Kingdom, Canada and 7 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Yes. Results are posted in the registry (first posted 28 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs (time frame: Baseline through study termination, an average of 12.1 months). 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 28 May 2024.