E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Mitochondrial Myopathy |
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E.1.1.1 | Medical condition in easily understood language |
Group of disorders associated with changes in genetic material found within the DNA of mitochondria (mtDNA) or in genes outside the mitochondria (nuclear DNA), mainly affecting the skeletal muscle
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027710 |
E.1.2 | Term | Mitochondrial myopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate long-term safety and tolerability of REN001 in subjects with PMM. |
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E.2.2 | Secondary objectives of the trial |
To assess subjects with mtDNA-PMM who are receiving long-term treatment with REN001 in terms of PMM associated symptoms, pain severity and interference, exercise endurance, quality of life (QoL), patient global impression of change (PGIC) and patient global impression of severity (PGIS) for muscle and fatigue, and work productivity. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. mtDNA-PMM subjects: Completed treatment in the STRIDE study or participated in Study REN001-101, and in the opinion of the Investigator and Sponsor have 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. 2. Have PMM which continues to be primarily characterized by exercise intolerance or active muscle pain. 3. Willing and able to swallow gelatin capsules. 4. 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. 5. Signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 6. 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 last dose of study drug. Males with partners who are WOCBP must also use contraception from baseline through to 14 weeks after last dose of study drug. If subjects are transferred to a commercial supply of REN001 they must be advised to adhere to the contraceptive requirements |
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E.4 | Principal exclusion criteria |
1. Anticipated to need a PPAR agonist other than REN001 during the study. 2. Anticipated to need drugs during the study with a narrow therapeutic index and Breast Cancer Resistant Protein (BCRP) mediated absorption, distribution, metabolism and excretion (ADME). 3. Intent to donate blood, or blood components during the study or within one month after completion of the study. 4. Current drug dependency. Use of opiates/cannabis for medical reasons is acceptable with prescription evidence or at the Investigator’s discretion. 5. Current alcohol dependency. 6. Any medical or psychiatric condition or laboratory abnormality 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. 7. Pregnant or nursing females. |
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E.5 End points |
E.5.1 | Primary end point(s) |
For mtDNA and nDNA subjects: •Number and severity of adverse events (AE) •Number of AEs leading to study drug discontinuation •Number of serious adverse events (SAEs) •Number of adverse events of special interest (AESIs) •Number of AEs leading to death
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
For mtDNA and nDNA subjects: Absolute values, changes from baseline, and incidence of potentially clinically significant changes in: •Laboratory safety tests •Electrocardiograms (ECG) •Supine vital signs •Eye assessments
For mtDNA subjects: Absolute values and changes from baseline in: •Distance walked during the 12-Minute Walk Test (12MWT) •Modified Fatigue Impact Scale (MFIS) total scores and sub-scale scores •Patient Global Impression of Severity (PGIS) scores for fatigue and muscle symptoms •Brief Pain Inventory (BPI) pain severity and pain interference scores •Patient Reported Outcomes Measurement Informal System (PROMIS) Short Form-Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue 13a scores •36 Item Short Form Health Survey (SF-36) domain scores (7-day recall) •Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) scores •First 6-minute walk distance and last 6-minute walk distance •Phenotypic description question •PGIC (muscle and fatigue symptoms) scores
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
New Zealand |
Australia |
Canada |
United Kingdom |
Belgium |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |