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

Primary Mitochondrial Myopathy Clinical Trial

— STRIDE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04535609
• Other study ID #: REN001-201
• Status: Completed
• Phase: Phase 2
• Start date: May 21, 2021
• Est. completion date: October 5, 2023

Study information

• Verified date: April 2024
• Source: Reneo Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: October 5, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mitochondrial Myopathies
• Muscular Diseases
• Primary Mitochondrial Myopathy

Intervention

Drug:
• Mavodelpar
Once daily
• Placebo
Once daily

Locations

Country	Name	City	State
Australia	PARC Clinical Research	Adelaide	South Australia
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Belgium	University Hospital Leuven	Leuven
Canada	M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)	Calgary	Alberta
Canada	Adult Metabolic Diseases Clinic, Vancouver General Hospital	Vancouver	British Columbia
Czechia	General University Hospital in Prague	Prague
Denmark	Rigshospitalet, University of Copenhagen	Copenhagen
France	Centre Hospitalier Universitaire d' Angers	Angers	Pays De La Loire
France	Hôpital Neurologique Pierre Wertheimer	Bron
France	Hôpital Roger Salengro	Lille	Hauts De France
France	CHU de Nice	Nice
France	Hôpital Pitié-Salpêtrière	Paris	Ile-de-France
France	Hôpitaux Universitaires de Strasbourg	Strasbourg	Grand Est
Germany	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
Hungary	Semmelweis University Insitute of Genomics and Rare Disorders	Budapest
Hungary	University of Pécs Clinical Centre, Department of Neurology	Pécs
Italy	IRCCS Istituto delle Scienze Neurologiche	Bologna
Italy	A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari	Messina	Sicilia
Italy	Fondazione IRCCS Istituto Neurologico "Carlo Besta" UOC Genetica Medica e Neurogenetica	Milano	Lombardia
Italy	Azienda Ospedaliero-Universitaria Pisana Dipartimento di specialita' mediche UOC Neurologia	Pisa	Toscana
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit	Roma	Lazio
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
New Zealand	University of Auckland	Auckland
Norway	Haukeland University Hospital	Bergen
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United Kingdom	Queen Square Centre for Neuromuscular Diseases	London	Greater London
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Greater Manchester
United States	Akron Children's Hospital	Akron	Ohio
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas SouthWestern Medical Center	Dallas	Texas
United States	Myology Institute, University of Florida	Gainesville	Florida
United States	Centre for the Treatment of Pediatric Neurodegenerative Disease, University of Texas McGovern Medical School	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	Columbia University Irving Medical Center	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Reneo Pharma Ltd

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Italy,  Netherlands,  New Zealand,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Distance Walked During a 12 Minute Walk Test	Distance walked in meters	Baseline to Week 24
Secondary	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