Primary mitochondrial myopathy MedDRA version: 20.0 Level: PT Classification code 10027710 Term: Mitochondrial myopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: REN001
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: REN001
Current Sponsor code: REN001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100
Sponsors
Reneo Pharma Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for inclusion in the study: 1. Males or females aged 16 years or older. 2. Established diagnosis of PMM according to the 2016 Rome Consensus recommendations (Mancuso, McFarland, Klopstock, & Hirano, 2017). 3. A score of 2-4 on Question 5 Section III of NMDAS from subject's medical history or at screening whichever is most relevant. 4. Either a confirmed m.3243A>G mutation or other mtDNA defects, with myopathy. 5. Have no changes to their exercise regimen within 30 days prior to Day 1 and be willing to remain on the same exercise regimen for the duration of the study. 6. Subjects must be ambulatory and able to perform the study exercise tests independently. 7.Subjects must be able to remain on stable medication through the study and specifically must not commence or have changes in medication for diabetes. 8. Have adequate kidney function defined as an estimated glomerular filtration rate (eGFR) = 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (Levey, et al., 2009) at Screening and Baseline. 9. Be able to swallow capsules. 10. Females should be either of non-child-bearing potential or must agree to use a highly effective method of contraception from Screening. Males with partners who are WOCBP must also use contraception from Baseline. 11. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. Are the trial subjects under 18? yes Number of subjects for this age range: 3 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. Participation in a prior REN001 (previously known as HPP-593) study. 2. Employee of the study site or of the Sponsor’s company or delegates. 3. Documented evidence of ongoing rhabdomyolysis. 4. Currently taking or anticipated to need a PPAR agonist during the study. 5. Subjects with motor abnormalities other than related to the mitochondrial disease that may interfere with the outcome measures. 6. Treatment with an investigational drug within 3 months prior to Day 1. 7. Currently taking or anticipated to need a prescription and/or non-prescription drug that might interfere with the study endpoints. 8. 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). 9. Subjects with diabetes who require treatment with insulin who are unwilling to undertake glucose monitoring for at least the first 12 weeks of dosing or in the Investigators opinion will not be able to adequately maintain glucose homeostasis. 10. Subjects with a history of cancer. A history of in situ basal cell carcinoma in the skin is allowed. 11. Have been hospitalised within the 3 months prior to Screening for any major medical condition (as deemed by the Principal Investigator). 12. Clinically significant cardiac disease or ECG abnormalities that in the opinion of the Principal Investigator should exclude the subject from enrolment into the study. 13. Any condition possibly reducing drug absorption (e.g., gastrectomy or serious GI dysmotility). 14. Subjects who have poor nutritional status as determined by the Investigator. 15. History of clinically significant liver disease and/or liver function tests (AST, ALT, total Bilirubin) >1.5 x ULN. Subjects with LFTs >1.5 x ULN and 3 x ULN). Subjects with CPK > 3 x ULN and < 5 x ULN at Screening may be retested once. 17. Subjects with positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C or human immunodeficiency virus (HIV) at Screening. 18. Pregnant or nursing females. 19. History of sensitivity to PPAR agonists. 20. Subjects who are taking anticoagulants that would preclude muscle biopsy. 21. Donation or intent to donate blood, or blood components during the study or within one month after completion of the study. 22. Subjects with a history of drug abuse or with a positive urine drug screen at Screening. Positive results for opiates and/or benzodiazepines will only be allowed if supported by a corresponding prescription from a medically qualified person. 23. History of regular alcohol consumption exceeding 14 units/week (1 unit = 75 mL of wine or 250 mL of beer or 25 mL of spirits) within 6 months of Screening. 24. Inabilit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of REN001 in subjects with PMM, during 12 weeks of treatment;Secondary Objective: 1. To evaluate the safety and tolerability of REN001 in subjects with PMM, during 48 weeks of treatment. 2. To investigate pharmacokinetics of REN001 in subjects with PMM treated for 12 weeks with REN001, administered as a capsule, using a population pharmacokinetic methodology. 3. To investigate the pharmacodynamic effects of REN001 in subjects with PMM treated for 12 weeks;Primary end point(s): • Number and severity of adverse events;Timepoint(s) of evaluation of this end point: Baseline to follow-up visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Absolute values, changes from baseline (at 12 and 48 weeks if applicable) and incidence of clinically significant changes in: • Laboratory safety tests • Electrocardiograms • Supine vital signs Pharmacokinetic • REN001 plasma concentrations using population pharmacokinetic methodology • Identification of metabolites using pooled plasma Pharmacodynamic Absolute values and changes from baseline in serum biomarkers: • FGF-21 (Baseline and Week 12) • GDF-15 (Baseline and Week 12) Absolute values and changes from baseline in acylcarnitine panel (Baseline and Week 12) Changes from baseline in muscle histopathology (Week 12);Timepoint(s) of evaluation of this end point: Safety Baseline and weeks 1, 2, 4, 8, 12, 16, 20, 24, 36 and 48 (Weeks 16 to 48 apply only to subjects who take part in optional part B), and follow-up Pharmacokinetic Baseline to Week 12 Pharmacodynamic Baseline and Week 12 | — |
Countries
United Kingdom
Contacts
Public ContactLynn Purkins
Reneo Pharma Ltd.
Outcome results
None listed