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

NCT ID: NCT04535609

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 213 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-21
• Study Completion Date: 2023-10-05

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.

Conditions

Primary Mitochondrial Myopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Mavodelpar

Once daily

Group Type: EXPERIMENTAL

Mavodelpar

Intervention Type: DRUG

Once daily

Matched placebo

Once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Once daily

Interventions

Mavodelpar

Once daily

Intervention Type: DRUG

Placebo

Once daily

Intervention Type: DRUG

Other Intervention Names

REN001

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Reneo Pharma Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amel Karaa, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital (MGH)

Locations

University of California, San Diego

La Jolla, California, United States

Myology Institute, University of Florida

Gainesville, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Columbia University Irving Medical Center

New York, New York, United States

Akron Children's Hospital

Akron, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Texas SouthWestern Medical Center

Dallas, Texas, United States

Centre for the Treatment of Pediatric Neurodegenerative Disease, University of Texas McGovern Medical School

Houston, Texas, United States

Royal North Shore Hospital

St Leonards, New South Wales, Australia

PARC Clinical Research

Adelaide, South Australia, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

University Hospital Leuven

Leuven, , Belgium

M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)

Calgary, Alberta, Canada

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

Centre Hospitalier Universitaire d' Angers

Angers, Pays de la Loire Region, France

Hôpital Neurologique Pierre Wertheimer

Bron, , France

CHU de Nice

Nice, , France

Hôpital Pitié-Salpêtrière

Paris, Île-de-France Region, 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

Semmelweis University Insitute of Genomics and Rare Disorders

Budapest, , Hungary

University of Pécs Clinical Centre, Department of Neurology

Pécs, , Hungary

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit

Rome, Lazio, Italy

Fondazione IRCCS Istituto Neurologico "Carlo Besta" UOC Genetica Medica e Neurogenetica

Milan, Lombardy, Italy

A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari

Messina, Sicily, Italy

Azienda Ospedaliero-Universitaria Pisana Dipartimento di specialita' mediche UOC Neurologia

Pisa, Tuscany, Italy

IRCCS Istituto delle Scienze Neurologiche

Bologna, , Italy

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

University of Auckland

Auckland, , New Zealand

Haukeland University Hospital

Bergen, , Norway

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Queen Square Centre for Neuromuscular Diseases

London, Greater London, United Kingdom

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

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

REN001-201

Identifier Type: -

Identifier Source: org_study_id