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

NCT05267574 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: REN001-202
• Study Type: interventional
• Target: 155
• Locations: 12 countries
• Sites: 29

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.

Conditions

Primary Mitochondrial Myopathy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Mild, Moderate, Severe TEAEs, TEAEs Leading to Study Discontinuation, All TEAEs and All TESAEs

  Number of participants with AEs and severity

  Baseline through study termination, an average of 12.1 months

Secondary Outcomes (9)

• Absolute Values, Changes From Baseline, and Incidence of Potentially Clinically Significant Changes in Laboratory Safety Tests, Electrocardiograms, Supine Vital Signs, and Eye Assessments

  Study Termination

• Change in Distance Walked During a 12 Minute Walk Test

  Baseline to Month 24

• Change in Modified Fatigue Impact Scale (MFIS) Score

  Baseline to Month 24

• Change in Patient Global Impression of Severity (PGIS) Score

  Baseline to Month 24

• Change in Brief Pain Inventory (BPI) Score

  Baseline to Month 24

Study Arms (1)

REN001

EXPERIMENTAL

100 mg once daily

Drug: REN001

Interventions

REN001 DRUG

Once daily dosing

REN001

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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 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.

Sponsors & Collaborators

• Reneo Pharma Ltd: lead

Study Sites (29)

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, 3000, Belgium

Location

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

Calgary, Alberta, T2E 7Z4, Canada

Location

Vancouver General Hospital

Vancouver, V5Z 1M9, Canada

Location

Copenhagen Neuromuscular Center

Copenhagen, 2100, Denmark

Location

Hôpital Roger Salengro

Lille, Hauts-de-France, 59037, France

Location

Centre de Référence des Maladies Neuromusculaires

Angers, 49933, France

Location

Hôpital Neurologique

Bron, 69599, France

Location

Nice Teaching Hospital

Nice, France

Location

Hôpitaux Universitaires Pitié Salpêtrière

Paris, 75013, France

Location

CHU de Strasbourg- Hopital de Hautepierre

Strasbourg, 6700, 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

Pécs, 7624, Hungary

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit

Rome, Lazio, 00168, Italy

Location

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

Messina, Sicily, 98125, Italy

Location

IRCCS Institute of Neurological Sciences of Bologna

Bologna, 40139, Italy

Location

Istituto Nazionale Neurologico Carlo Besta

Milan, 20100, Italy

Location

U.O. di Neurologia - Neurofisiopatologia

Pisa, 56100, Italy

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525EX, Netherlands

Location

Centre for Brain Research Neurogenetic Clinic

Grafton, Auckland, 1042, New Zealand

Location

Hospital Universitario 12 de Octubre

Madrid, 20841, 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

The Newcastle upon Tyne Hospitals NHS Foundation Trust

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

Location

Salford Royal NHS Foundation Trust

Salford, M5 5AP, 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

• Grainne Gorman, MD

  Newcastle Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 4, 2022
• Study Start: February 1, 2022
• Primary Completion: December 14, 2023
• Study Completion: January 31, 2024
• Last Updated: May 28, 2024
• Results First Posted: May 28, 2024

Record last verified: 2024-04

Locations

DE (2); DK (1); NL (1); NZ (1); CA (2); HU (2); FR (6); AU (3); IT (5); BE (1); ES (2); GB (3)