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

A Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of 24 Weeks Treatment With REN001 in Patients With Primary Mitochondrial Myopathy

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.

Study Overview

• Status: Completed
• Conditions: Primary Mitochondrial Myopathy
• Intervention / Treatment: Drug: Placebo; Drug: Mavodelpar

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trial Coordinator; Phone Number: +44 (0) 1304 809360; Email: clintrialinfo@reneopharma.com

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • PARC Clinical Research
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Leuven, Belgium, 3000B
    • University Hospital Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2E 7Z4
      • M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Adult Metabolic Diseases Clinic, Vancouver General Hospital
• Czechia
  • Prague, Czechia, 12808
    • General University Hospital in Prague
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, University of Copenhagen
• France
  • Bron, France, 69599
    • Hôpital Neurologique Pierre Wertheimer
  • Nice, France, 06202
    • CHU de Nice
  • Grand Est
    • Strasbourg, Grand Est, France, 67200
      • Hôpitaux Universitaires de Strasbourg
  • Hauts De France
    • Lille, Hauts De France, France, 59037
      • Hopital Roger Salengro
  • Ile-de-France
    • Paris, Ile-de-France, France, 75651
      • Hôpital Pitié-Salpétrière
  • Pays De La Loire
    • Angers, Pays De La Loire, France, 49933
      • Centre Hospitalier Universitaire d' Angers
• Germany
  • Bonn, Germany, 53127
    • University Hospital Bonn Clinic and Polyclinic for Neurology
  • Munich, Germany, 80336
    • Medical Center of the University of Munich Friedrich Baur Institute at the Neurological Clinic and Polyclinic
• Hungary
  • Budapest, Hungary, 1082
    • Semmelweis University Insitute of Genomics and Rare Disorders
  • Pécs, Hungary, 7623
    • University of Pécs Clinical Centre, Department of Neurology
• Italy
  • Bologna, Italy, 40139
    • IRCCS Istituto delle Scienze Neurologiche
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit
  • Lombardia
    • Milano, Lombardia, Italy, 20126
      • Fondazione IRCCS Istituto Neurologico "Carlo Besta" UOC Genetica Medica e Neurogenetica
  • Sicilia
    • Messina, Sicilia, Italy, 98125
      • A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • Azienda Ospedaliero-Universitaria Pisana Dipartimento di specialita' mediche UOC Neurologia
• Netherlands
  • Nijmegen, Netherlands, 6525EX
    • Radboud Universitair Medisch Centrum
• New Zealand
  • Auckland, New Zealand, 1023
    • University of Auckland
• Norway
  • Bergen, Norway, N-5053
    • Haukeland University Hospital
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, 08041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46026
    • Hospital Universitari I Politecnic La Fe
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3BG
      • Queen Square Centre for Neuromuscular Diseases
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal NHS Foundation Trust
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
  • Florida
    • Gainesville, Florida, United States, 32608
      • Myology Institute, University of Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77025
      • Centre for the Treatment of Pediatric Neurodegenerative Disease, University of Texas McGovern Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matched placebo; Once daily	Drug: Placebo; Once daily
Experimental: Mavodelpar; Once daily	Drug: Mavodelpar; Once daily; Other Names: REN001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Distance Walked During a 12 Minute Walk Test	Distance walked in meters	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PROMIS Short Form - Fatigue 13a (FACIT-fatigue) Scores	The PROMIS is a 13-item questionnaire to describe fatigue and its impact upon daily activities and function. Each item is scored between 1=Not At All and 5=Very Much	Baseline to Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events, serious adverse events, and withdrawals due to adverse events	Number and Severity	Baseline to Week 24
Change in number of sit to stands completed during a 30 second sit to stand (30STS) test	Number completed	Baseline to Week 24
Change in step counts as measured by a pedometer	Number of steps	Baseline to Week 24
Change in Modified Fatigue Impact Scale (MFIS) score	The MFIS is a 21-item questionnaire to describe the impact of fatigue on physical, cognitive, and psychosocial functioning. The questionnaire includes 9 physical, 10 cognitive and 2 psychosocial items with each item scored between 0=Never and 4=Almost Always	Baseline to Week 24
Change in Patient Global Impression of Severity (PGIS) score	The PGIS is a 2-item questionnaire to describe the severity of fatigue and muscle symptoms. Each item is scored as Very Much Worse, Moderately Worse, Minimally Worse, No Change, Minimally Improved, Moderately Improved, or Very Much Improved	Baseline to Week 24
Change in 36-Item Short Form Health Survey (SF-36) score	The SF-36 is a 36-item questionnaire to describe health status and quality of life. The questionnaire includes 8 domains (vitality, physical functioning, bodily pain, general health perceptions, role limitations due to physical health, role limitations due to emotional health, social role functioning, and mental health). Items are scored, summed into domains, and transformed into a scale of 0-100	Baseline to Week 24
Change in Brief Pain Inventory (BPI) score	The BPI is a 15-item questionnaire to describe severity of pain and its interference on functioning. The questionnaire includes 4 pain severity items each scored between 0=No Pain and 10= Pain, and 7 pain interference items each scored between 0=Does not Interfere and 10=Completely Interferes	Baseline to Week 24
Change Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) score	The WPAI:SHP is a 6-item questionnaire to describe impairment in work and activities due to a certain disease. Items are scored, summed, and transformed into a scale of 0-100%	Baseline to Week 24
Change in Patient Global Impression of Change (PGIC) score	The PGIC is a 2-item questionnaire to describe the change in fatigue and muscle symptoms since starting the study. Each item is scored as Very Much Worse, Moderately Worse, Minimally Worse, No Change, Minimally Improved, Moderately Improved, or Very Much Improved	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Reneo Pharma Ltd
• Investigators: Principal Investigator: Amel Karaa, MD, Massachusetts General Hospital (MGH)

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2021
• Primary Completion (Actual): September 12, 2023
• Study Completion (Actual): October 5, 2023

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Mitochondrial Diseases; Muscular Diseases; Mitochondrial Myopathies
• Other Study ID Numbers: REN001-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No