A DOUBLE-BLIND, PLACEBO-CONTROLLED, STUDY TO EVALUATE THE EFFICACY AND SAFETY OF 24 WEEKS TREATMENT WITH REN001 IN PATIENTS WITH PRIMARY MITOCHONDRIAL MYOPATHY (PMM)
- Conditions
- PMMPrimary Mitochondrial Myopathy1002929910029305
- Registration Number
- NL-OMON51665
- Lead Sponsor
- Reneo Pharma Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 21
1. Subjects aged 18 years or older with PMM
2. A confirmed PMM diagnosis due to known pathogenic gene mutation or deletion
of the mitochondrial genome.
3. Documented PMM primarily characterized by exercise intolerance or active
muscle pain.
4. Subjects must be ambulatory and able to perform the 12MWT independently
(walking aids are allowed).
5. Distance walked of <=1000 meters at Screening in the 12MWT (must be obtained
at least 4 weeks before randomization).
6. 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.
7. Be willing and able to swallow gelatin capsules.
8. 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.
9. Concomitant medications (including supplements) must be stable for at least
1 month prior to enrolment and throughout participation in the study.
10. For subjects under 25 years of age, confirmation of bone growth plate
closure by wrist radiograph
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.
1. Participation in a prior REN001 study.
2. Currently taking or anticipated to need a PPAR agonist during the study.
3. Bone deformities or motor abnormalities other than related to the
mitochondrial myopathy that may interfere with the outcome measures.
4. Treatment with an investigational drug within 3 months or 5 drug half-lives,
whichever is longer, prior to Day 1.
5. Anticipated to need a prescription and/or non-prescription drug that might
interfere with the study endpoints
6. Currently taking drugs with a narrow therapeutic index and BCRP mediated
ADME
7. Clinically significant kidney disease or impairment with an eGFR less than
60ml/min/1.73m2 using the CKD-EPI creatinine equation at Screening.
8. 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.
9. Uncontrolled diabetes and/or a Screening HbA1c of >=11%.
10. Uncontrolled epilepsy.
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.
12. A history of cancer. A history of in situ basal cell carcinoma in the skin
is allowed.
13. Have been hospitalized within the 3 months prior to Screening for any major
medical condition (as deemed by the Investigator).
14. Clinically significant cardiac disease and/or clinically significant ECG
abnormalities including a screening QTcF of >= 450 msec, 2nd degree heart
block, symptomatic tachyarrhythmia or unstable arrythmia that in the opinion of
the Investigator should exclude the subject from completing exercise tests
(i.e. study 12 MWT and 30 STS tests).
15. Any condition possibly reducing drug absorption.
16. Evidence of hospitalization for rhabdomyolysis within the year prior to
enrolment.
17. Positive HBsAg and HBcAb at screening or positive for hepatitis C or HIV at
Screening..
18. Pregnant or nursing females.
19. History of sensitivity to PPAR agonists.
20. Donation or intent to donate blood, or blood components during the study or
within one month after completion of the study.
21. A history of drug dependency. Use of opiates/cannabis for medical reasons
is acceptable with prescription evidence or at the Investigators discretion.
22. A history of alcohol dependency.
23. Significant impairment due to central or peripheral nervous system
involvement that would interfere with the exercise tests.
24. Significant weakness not caused by the underlying primary muscle disease
such as post stroke or neurogenic weakness.
25. Have had an organ transplant.
26. Are not eligible or have a contraindication for cataract surgery.
27. A history of osteoporosis as evidenced by non-traumatic (stress) fractures
or a prior T-score of -2.5 or worse which has not been adequately addressed.
28. Inability to comprehend or unwilling to follow the study requirements
including restrictions on treatments, attendance at the study center,
completion of questionnaires and participation in laboratory testing as called
for by the protocol.
29. Any other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or investig
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change from baseline in distance walked during the 12 minute walk test.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Change from Baseline in the Modified Fatigue Impact Scale (MFIS) Physical<br /><br>sub-scale score;<br /><br>Patient Global Impression of Change (PGIC) score (muscle symptoms).</p><br>