Clinical trial NCT04535609: An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Mitochondrial Myopathy
Lead sponsor: OnKure, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-02
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in Distance Walked During a 12 Minute Walk Test
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change in PROMIS Short Form - Fatigue 13a (FACIT-fatigue) Scores
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Gainesville
country: United States
facility: Myology Institute, University of Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas SouthWestern Medical Center
state: Texas
city: Houston
country: United States
facility: Centre for the Treatment of Pediatric Neurodegenerative Disease, University of Texas McGovern Medical School
state: Texas
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: PARC Clinical Research
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Calgary
country: Canada
facility: M.A.G.I.C. Clinic (Metabolics and Genetics in Calgary)
state: Alberta
city: Vancouver
country: Canada
facility: Adult Metabolic Diseases Clinic, Vancouver General Hospital
state: British Columbia
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
state: Grand Est
city: Lille
country: France
facility: Hôpital Roger Salengro
state: Hauts De France
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
state: Ile-de-France
city: Angers
country: France
facility: Centre Hospitalier Universitaire d' Angers
state: Pays De La Loire
city: Bron
country: France
facility: Hôpital Neurologique Pierre Wertheimer
city: Nice
country: France
facility: CHU de Nice
city: Bonn
country: Germany
facility: University Hospital Bonn Clinic and Polyclinic for Neurology
city: Munich
country: Germany
facility: Medical Center of the University of Munich Friedrich Baur Institute at the Neurological Clinic and Polyclinic
city: Budapest
country: Hungary
facility: Semmelweis University Insitute of Genomics and Rare Disorders
city: Pécs
country: Hungary
facility: University of Pécs Clinical Centre, Department of Neurology
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS Neurophysiopathology Unit
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico "Carlo Besta" UOC Genetica Medica e Neurogenetica
state: Lombardia
city: Messina
country: Italy
facility: A.O.U Policlinico di Messina U.O.C Neurologia e Malattie Neuromuscolari
state: Sicilia
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana Dipartimento di specialita' mediche UOC Neurologia
state: Toscana
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Auckland
country: New Zealand
facility: University of Auckland
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: London
country: United Kingdom
facility: Queen Square Centre for Neuromuscular Diseases
state: Greater London
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
state: Greater Manchester
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
state: Tyne And Wear
Study officials:
affiliation: Massachusetts General Hospital (MGH)
name: Amel Karaa, MD
role: PRINCIPAL_INVESTIGATOR
References: