A Study of the Efficacy and Safety of 24 Week Treatment With REN001 in Patients With Primary Mitochondrial Myopathy (STRIDE)

• ClinicalTrials.gov Identifier: NCT04535609
• Recruitment Status: Recruiting
• First Posted: September 2, 2020
• Last Update Posted: December 8, 2022
• Sponsor: Reneo Pharma Ltd
• Information provided by (Responsible Party): Reneo Pharma Ltd

Tracking Information

• First Submitted Date: August 27, 2020
• First Posted Date: September 2, 2020
• Last Update Posted Date: December 8, 2022
• Actual Study Start Date: May 21, 2021
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2020)

Change from Baseline in distance walked during the Walk Test [ Time Frame: Week 24 ]

Distance walked in meters

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2020)

• Change from Baseline at Week 24 in the Modified Fatigue Impact Scale (MFIS) physical sub-scale score [ Time Frame: Week 24 ]
  Physical Scale 0-36 scoring
• Patient Global Impression of Change (PGIC) score at Week 24 [ Time Frame: Week 24 ]
  7 point scale: Very much improved, Moderately improved, Minimally improved, No change, Minimally worse, Moderately worse, Very much worse

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 27, 2020)

• Incidence and severity of adverse events, serious adverse events, and withdrawals due to adverse events [ Time Frame: Baseline to Week 24 ]
  Number and Severity
• Change from Baseline in number of sit to stands in the sit to stand test [ Time Frame: Week 24 ]
  Individual counts
• Change from Baseline in number of steps [ Time Frame: Week 24 ]
  Step count from pedometer
• Change from Baseline in Patient Global Impression of Severity (PGIS) score [ Time Frame: Week 24 ]
  5 point scale: Absent, Mild, Moderate, Severe, Very Severe
• Change from Baseline in MFIS total, cognitive and psychosocial sub-scale scores [ Time Frame: Week 24 ]
  Total MFIS 0-84, cognitive 0-40, psychosocial 0-8
• Change from Baseline in Brief Pain Inventory pain severity and pain interference scores [ Time Frame: Week 24 ]
  Numerical rating scale 0-10

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Study of the Efficacy and Safety of 24 Week Treatment With REN001 in Patients With Primary Mitochondrial Myopathy
• Official Title: A Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of 24 Weeks Treatment With REN001 in Patients With Primary Mitochondrial Myopathy
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary Mitochondrial Myopathy

Intervention

• Drug: REN001
  Once daily
• Drug: Placebo
  Once daily

Study Arms

• Experimental: REN001
  Once daily
  Intervention: Drug: REN001
• Placebo Comparator: Matched placebo
  Once daily
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 27, 2020): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trial Coordinator; +44 (0) 1304 809360; clintrialinfo@reneopharma.com

• Listed Location Countries: Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Italy, Netherlands, New Zealand, Norway, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04535609
• Other Study ID Numbers: REN001-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Reneo Pharma Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Reneo Pharma Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Amel Karaa, MD; Massachusetts General Hospital (MGH)

• PRS Account: Reneo Pharma Ltd
• Verification Date: December 2022