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

NCT04535609 | Completed Phase 2 Results FDA Drug

• 1 other identifier: REN001-201
• Study Type: interventional
• Target: 213
• Locations: 15 countries
• Sites: 41

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

Outcome Measures

Primary Outcomes (1)

• Change in Distance Walked During a 12 Minute Walk Test

  Distance walked in meters

  Baseline to Week 24

Secondary Outcomes (1)

• Change in PROMIS Short Form - Fatigue 13a (FACIT-fatigue) Scores

  Baseline to Week 24

Study Arms (2)

Mavodelpar

EXPERIMENTAL

Once daily

Drug: Mavodelpar

Matched placebo

PLACEBO COMPARATOR

Once daily

Drug: Placebo

Interventions

Mavodelpar DRUG

Once daily

Also known as: REN001

Mavodelpar

Placebo DRUG

Once daily

Matched placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Reneo Pharma Ltd: lead

Study Sites (41)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Myology Institute, University of Florida

Gainesville, Florida, 32608, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas SouthWestern Medical Center

Dallas, Texas, 75390, United States

Location

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

Houston, Texas, 77025, United States

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

PARC Clinical Research

Adelaide, South Australia, 5000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

University Hospital Leuven

Leuven, 3000B, Belgium

Location

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

Calgary, Alberta, T2E 7Z4, Canada

Location

Adult Metabolic Diseases Clinic, Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

General University Hospital in Prague

Prague, 12808, Czechia

Location

Rigshospitalet, University of Copenhagen

Copenhagen, 2100, Denmark

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, Grand Est, 67200, France

Location

Hôpital Roger Salengro

Lille, Hauts-de-France, 59037, France

Location

Centre Hospitalier Universitaire d' Angers

Angers, Pays de la Loire Region, 49933, France

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69599, France

Location

CHU de Nice

Nice, 06202, France

Location

Hôpital Pitié-Salpêtrière

Paris, Île-de-France Region, 75651, France

Location

University Hospital Bonn Clinic and Polyclinic for Neurology

Bonn, 53127, Germany

Location

Medical Center of the University of Munich Friedrich Baur Institute at the Neurological Clinic and Polyclinic

Munich, 80336, Germany

Location

Semmelweis University Insitute of Genomics and Rare Disorders

Budapest, 1082, Hungary

Location

University of Pécs Clinical Centre, Department of Neurology

Pécs, 7623, Hungary

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit

Rome, Lazio, 00168, Italy

Location

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

Milan, Lombardy, 20126, Italy

Location

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

Messina, Sicily, 98125, Italy

Location

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

Pisa, Tuscany, 56126, Italy

Location

IRCCS Istituto delle Scienze Neurologiche

Bologna, 40139, Italy

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525EX, Netherlands

Location

University of Auckland

Auckland, 1023, New Zealand

Location

Haukeland University Hospital

Bergen, N-5053, Norway

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 08041, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Queen Square Centre for Neuromuscular Diseases

London, Greater London, WC1N 3BG, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, Greater Manchester, M6 8HD, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

Results Point of Contact

• Title: Alex Dorenbaum, MD, Chief Medical Officer
• Organization: Reneo Pharmaceuticals, Inc.

adorenbaum@reneopharma.com

(415) 328-9115

Study Officials

• Amel Karaa, MD

  Massachusetts General Hospital (MGH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 2, 2020
• Study Start: May 21, 2021
• Primary Completion: September 12, 2023
• Study Completion: October 5, 2023
• Last Updated: May 8, 2024
• Results First Posted: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); CA (2); CZ (1); ES (3); FR (6); US (9); NL (1); NZ (1); NO (1); AU (3); DK (1); DE (2); HU (2); BE (1); GB (3)