An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients
- Registration Number
- NCT04535609
- Lead Sponsor
- Reneo Pharma Ltd
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 213
- 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).
- 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.
- Documented PMM primarily characterized by exercise intolerance or active muscle pain.
- Subjects must be ambulatory and able to perform the walking tests independently (walking aids are allowed).
- 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.
- 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.
- Concomitant medications (including supplements) must be stable for at least 1 month prior to enrolment and throughout participation in the study.
- 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:
- Participation in a prior REN001 (previously known as HPP-593) study.
- Currently taking or anticipated to need a PPAR agonist during the study.
- Subjects with bone deformities or motor abnormalities other than related to the mitochondrial myopathy that may interfere with the outcome measures.
- 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.
- 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.
- Subjects with uncontrolled diabetes and/or a Screening HbA1c of ≥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. (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.)
- Subjects with a history of cancer. A history of in situ basal cell carcinoma in the skin is allowed.
- 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.
- Evidence of hospitalization for rhabdomyolysis within the year prior to enrolment.
- Pregnant or nursing females.
- History of sensitivity to PPAR agonists.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mavodelpar Mavodelpar Once daily Matched placebo Placebo Once daily
- Primary Outcome Measures
Name Time Method Change in Distance Walked During a 12 Minute Walk Test Baseline to Week 24 Distance walked in meters
- Secondary Outcome Measures
Name Time Method Change in PROMIS Short Form - Fatigue 13a (FACIT-fatigue) Scores Baseline to Week 24 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
Trial Locations
- Locations (41)
M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)
🇨🇦Calgary, Alberta, Canada
PARC Clinical Research
🇦🇺Adelaide, South Australia, Australia
IRCCS Istituto delle Scienze Neurologiche
🇮🇹Bologna, Italy
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Queen Square Centre for Neuromuscular Diseases
🇬🇧London, Greater London, United Kingdom
Myology Institute, University of Florida
🇺🇸Gainesville, Florida, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
University of Texas SouthWestern Medical Center
🇺🇸Dallas, Texas, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Centre for the Treatment of Pediatric Neurodegenerative Disease, University of Texas McGovern Medical School
🇺🇸Houston, Texas, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
University Hospital Leuven
🇧🇪Leuven, Belgium
Adult Metabolic Diseases Clinic, Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
General University Hospital in Prague
🇨🇿Prague, Czechia
Rigshospitalet, University of Copenhagen
🇩🇰Copenhagen, Denmark
Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, Grand Est, France
Hôpital Roger Salengro
🇫🇷Lille, Hauts De France, France
Hôpital Pitié-Salpêtrière
🇫🇷Paris, Ile-de-France, France
Centre Hospitalier Universitaire d' Angers
🇫🇷Angers, Pays De La Loire, France
Hôpital Neurologique Pierre Wertheimer
🇫🇷Bron, France
CHU de Nice
🇫🇷Nice, France
University Hospital Bonn Clinic and Polyclinic for Neurology
🇩🇪Bonn, Germany
Medical Center of the University of Munich Friedrich Baur Institute at the Neurological Clinic and Polyclinic
🇩🇪Munich, Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit
🇮🇹Roma, Lazio, Italy
Semmelweis University Insitute of Genomics and Rare Disorders
🇭🇺Budapest, Hungary
University of Pécs Clinical Centre, Department of Neurology
🇭🇺Pécs, Hungary
Fondazione IRCCS Istituto Neurologico "Carlo Besta" UOC Genetica Medica e Neurogenetica
🇮🇹Milano, Lombardia, Italy
A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari
🇮🇹Messina, Sicilia, Italy
Azienda Ospedaliero-Universitaria Pisana Dipartimento di specialita' mediche UOC Neurologia
🇮🇹Pisa, Toscana, Italy
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, Netherlands
University of Auckland
🇳🇿Auckland, New Zealand
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain
Haukeland University Hospital
🇳🇴Bergen, Norway
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Salford Royal NHS Foundation Trust
🇬🇧Salford, Greater Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, Tyne And Wear, United Kingdom