An Open Label, Long Term Safety Study of REN001 in Primary Mitochondrial Myopathy Patients (Stride Ahead)

NCT ID: NCT05267574

Last Updated: 2024-05-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2024-01-31

Brief Summary

This study is designed to evaluate the long-term safety and tolerability of REN001 administered once daily to subjects with PMM due to mitochondrial DNA mutations (mtDNA-PMM) or nuclear DNA mutations (nDNA-PMM). Subjects with mtDNA mutations will have previously completed Study REN001-201 or participated in Study REN001-101. Subjects with nDNA mutations who enroll in this study will be REN001- naïve.

Detailed Description

This study is designed to evaluate the long-term safety and tolerability of REN001 administered once daily to subjects with PMM due to mitochondrial DNA mutations (mtDNA=PMM) or nuclear DNA mutations (nDNA-PMM). Subjects with mtDNA mutations will have previously completed Study REN001-201 (which is referred to as the STRIDE study) or participated in Study REN001-101. Subjects with nDNA mutations who enroll in this study will be REN001- naïve.

Eligible subjects will be treated with REN001 100mg orally, once daily for 24 months. Following the baseline visit there are planned visits at at defined time points. A final follow-up telephone call will be made by the study centre to the subject approximately 30 days after the last dose of study drug.

Conditions

Primary Mitochondrial Myopathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

REN001

100 mg once daily

Group Type: EXPERIMENTAL

REN001

Intervention Type: DRUG

Once daily dosing

Interventions

REN001

Once daily dosing

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• mtDNA-PMM subjects: Completed treatment in STRIDE or was participating in Study REN001-101 when the study stopped due to the COVID-19 pandemic, and in the opinion of the Investigator and Sponsor had been compliant with the study requirements OR nDNA-PMM subjects: Subjects aged 18 years or older with known nuclear (nDNA) pathogenic variants with a major muscle phenotype consisting of objective myopathy with poor exercise tolerance. Proof of pathogenicity must be provided. Must be able to walk at least 100m in the screening 12MWT and the limitations in walk test must be primarily due to the energy deficit and not due to ataxia or any other condition. For subjects under 25 years old only: confirmation of bone growth plate closure by wrist radiograph.
• Have PMM which continues to be primarily characterized by exercise intolerance or active muscle pain.
• Willing and able to swallow the REN001 gelatin capsules.
• Concomitant medications (including supplements) intended for the treatment of PMM or other co-morbidities likely to remain stable throughout participation in the study where clinically possible.
• Signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception from baseline through to approximately 30 days after the last dose of study drug. Males with partners who are women of childbearing potential (WOCBP) must also use contraception from baseline through to 14 weeks after the last dose of study drug.

Exclusion Criteria

• Anticipated to need a peroxisome proliferator-activated receptor (PPAR) agonist other than REN001 during the study.
• Intent to donate blood, or blood components during the study or within one month after completion of the study.
• Current drug dependency. Use of opiates/cannabis for medical reasons is acceptable with prescription evidence or at the Investigator's discretion.
• Current alcohol dependency.
• Any medical, psychiatric or laboratory condition that may increase the risk associated with study participation or interfere with the interpretation of study results and, in the judgment of the Investigator and Medical Monitor, would make the subject inappropriate for entry into this study.
• Pregnant or nursing female

1. 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.

2. 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.

3. Subjects with uncontrolled diabetes and/or a Screening HbA1c of ≥11%.

4. 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.)

5. Subjects with a history of cancer. A history of in situ basal cell carcinoma in the skin is allowed.

6. Clinically significant cardiac disease and/or clinically significant ECG abnormalities such as 2nd degree heart block, symptomatic tachyarrhythmia or unstable arrhythmia (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.

• 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

Grainne Gorman, MD

Role: PRINCIPAL_INVESTIGATOR

Newcastle Hospital NHS Foundation Trust

Locations

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

Vancouver General Hospital

Vancouver, , Canada

Copenhagen Neuromuscular Center

Copenhagen, , Denmark

Hôpital Roger Salengro

Lille, Hauts-de-France, France

Centre de Référence des Maladies Neuromusculaires

Angers, , France

Hôpital Neurologique

Bron, , France

Nice Teaching Hospital

Nice, , France

Hôpitaux Universitaires Pitié Salpêtrière

Paris, , France

CHU de Strasbourg- Hopital de Hautepierre

Strasbourg, , 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

Pécs, , Hungary

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit

Rome, Lazio, Italy

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

Messina, Sicily, Italy

IRCCS Institute of Neurological Sciences of Bologna

Bologna, , Italy

Istituto Nazionale Neurologico Carlo Besta

Milan, , Italy

U.O. di Neurologia - Neurofisiopatologia

Pisa, , Italy

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Centre for Brain Research Neurogenetic Clinic

Grafton, Auckland, New Zealand

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

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

REN001-202

Identifier Type: -

Identifier Source: org_study_id