an efficacy and safety study of 24 week treatment with mavodelpar (ren001) in primary mitochondrial myopathy patients

Conditions: Primary Mitochondrial Myopathy

Summary: this is a randomized, double-blind, placebo-controlled, parallel group, multi-centre, study designed to investigate the efficacy and safety of ren001 administered once daily over a 24-week period to patients with pmm.


Eligibility criteria:
inclusion criteria: 1. subjects age 18 years or older with pmm as defined by the international workshop: outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adult (mancuso et al 2017). 2. a confirmed pmm diagnosis due to known pathogenic gene mutation or deletion of the mitochondrial genome. the sponsor may authorize local genetic testing at screening, if required, but results must be available prior to randomization of the subject. 3. documented pmm primarily characterized by exercise intolerance or active muscle pain. 4. subjects must be ambulatory and able to perform the walking tests independently (walking aids are allowed). 5. have no changes to any therapeutic exercise regimen within 30 days prior to day 1 and be willing to remain on the same therapeutic exercise regimen for the duration of the study. 6. females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception from screening through to 30 days after last dose in the study. males with partners who are wocbp must also use contraception. 7. concomitant medications (including supplements) must be stable for at least 1 month prior to enrolment and throughout participation in the study. 8. evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. exclusion: 1. participation in a prior ren001 (previously known as hpp-593) study. 2. currently taking or anticipated to need a ppar agonist during the study. 3. subjects with bone deformities or motor abnormalities other than related to the mitochondrial myopathy that may interfere with the outcome measures. 4. 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. 5. 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. 6. subjects with uncontrolled diabetes and/or a screening hba1c of ≥11%. 7. 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.) 8. subjects with a history of cancer. a history of in situ basal cell carcinoma in the skin is allowed. 9. clinically significant cardiac disease and/or clinically significant ecg abnormalities such as 2nd degree heart block, symptomatic tachyarrhythmia or unstable arrythmia (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. 10. evidence of hospitalization for rhabdomyolysis within the year prior to enrolment. 11. pregnant or nursing females. 12. history of sensitivity to ppar agonists.