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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05267574




Registration number
NCT05267574
Ethics application status
Date submitted
24/02/2022
Date registered
4/03/2022
Date last updated
28/05/2024

Titles & IDs
Public title
An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)
Scientific title
An Open-label, Multi-centre Study to Evaluate the Long-term Safety and Tolerability of REN001 in Subjects With Primary Mitochondrial Myopathy (PMM)
Secondary ID [1] 0 0
REN001-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Mitochondrial Myopathy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - REN001

Experimental: REN001 - 100 mg once daily


Treatment: Drugs: REN001
Once daily dosing
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs
Timepoint [1] 0 0
Baseline through study termination, an average of 12.1 months
Secondary outcome [1] 0 0
Absolute Values, Changes From Baseline, and Incidence of Potentially Clinically Significant Changes in Laboratory Safety Tests, Electrocardiograms, Supine Vital Signs, and Eye Assessments
Timepoint [1] 0 0
Study Termination
Secondary outcome [2] 0 0
Change in Distance Walked During a 12 Minute Walk Test
Timepoint [2] 0 0
Baseline to Month 24
Secondary outcome [3] 0 0
Change in Modified Fatigue Impact Scale (MFIS) Score
Timepoint [3] 0 0
Baseline to Month 24
Secondary outcome [4] 0 0
Change in Patient Global Impression of Severity (PGIS) Score
Timepoint [4] 0 0
Baseline to Month 24
Secondary outcome [5] 0 0
Change in Brief Pain Inventory (BPI) Score
Timepoint [5] 0 0
Baseline to Month 24
Secondary outcome [6] 0 0
Change in Patient Reported Outcomes Measurement Information System (PROMIS) Short Form - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 13a Scores
Timepoint [6] 0 0
Baseline to Month 24
Secondary outcome [7] 0 0
Change in 36-Item Short Form Health Survey (SF-36) Score
Timepoint [7] 0 0
Baseline to Month 24
Secondary outcome [8] 0 0
Change Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score
Timepoint [8] 0 0
Baseline to Month 24
Secondary outcome [9] 0 0
Change in Patient Global Impression of Change (PGIC) Score
Timepoint [9] 0 0
Baseline to Month 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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:

1. 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.
2. 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.
3. Subjects with uncontrolled diabetes and/or a Screening HbA1c of =11%.
4. 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.)
5. Subjects with a history of cancer. A history of in situ basal cell carcinoma in the skin is allowed.
6. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/01/2024
Sample size
Target
Accrual to date
Final
155
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [2] 0 0
PARC Clinical Research - Adelaide
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Canada
State/province [2] 0 0
Alberta
Country [3] 0 0
Canada
State/province [3] 0 0
Vancouver
Country [4] 0 0
Denmark
State/province [4] 0 0
Copenhagen
Country [5] 0 0
France
State/province [5] 0 0
Hauts De France
Country [6] 0 0
France
State/province [6] 0 0
Angers
Country [7] 0 0
France
State/province [7] 0 0
Bron
Country [8] 0 0
France
State/province [8] 0 0
Nice
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
France
State/province [10] 0 0
Strasbourg
Country [11] 0 0
Germany
State/province [11] 0 0
Bonn
Country [12] 0 0
Germany
State/province [12] 0 0
Munich
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
Hungary
State/province [14] 0 0
Pécs
Country [15] 0 0
Italy
State/province [15] 0 0
Lazio
Country [16] 0 0
Italy
State/province [16] 0 0
Sicilia
Country [17] 0 0
Italy
State/province [17] 0 0
Bologna
Country [18] 0 0
Italy
State/province [18] 0 0
Milan
Country [19] 0 0
Italy
State/province [19] 0 0
Pisa
Country [20] 0 0
Netherlands
State/province [20] 0 0
Nijmegen
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Greater London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Tyne And Wear
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Reneo Pharma Ltd
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05267574
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Grainne Gorman, MD
Address 0 0
Newcastle Hospital NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05267574