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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04944784
Other study ID # CY 5031
Secondary ID 2020-004040-29
Status Terminated
Phase Phase 3
First received
Last updated
Start date August 16, 2021
Est. completion date July 18, 2023

Study information

Verified date May 2024
Source Cytokinetics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS.


Description:

COURAGE-ALS is a Phase 3, double-blind, randomized, placebo-controlled trial of reldesemtiv in patients aged 18 to 80 with ALS. The screening and qualification period for the trial will be no more than 14 days in duration. Approximately 555 eligible ALS patients will be randomized (2:1) to receive the following dose of reldesemtiv or placebo (stratified by riluzole use/non-use and edaravone use/non-use) for the first 24 weeks (double-blind, placebo-controlled period): - 300 mg reldesemtiv twice a day for a 600 mg total daily dose (TDD) - Placebo twice daily At the end of the 24-week double-blind, placebo-controlled period, patients will transition to the active drug period, where all patients will receive the following dose of reldesemtiv for the next 24 weeks: - 300 mg reldesemtiv twice a day for a 600 mg TDD for patients who were not down titrated during the 24 weeks of blinded dosing - 150 mg reldesemtiv twice a day for a 300 mg TDD for patients who were down titrated during the 24 weeks of blinded dosing


Recruitment information / eligibility

Status Terminated
Enrollment 486
Est. completion date July 18, 2023
Est. primary completion date July 18, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility Key Inclusion Criteria: - Males or Females between the ages of 18 and 80 years of age, inclusive - Diagnosis of familial or sporadic ALS (defined as meeting the laboratory-supported probable, probable, or definite criteria for ALS according to the World Federation of Neurology El Escorial criteria). Patients who meet the possible criteria are eligible if they have lower motor neuron findings; those who have purely upper motor neuron findings are ineligible. - First symptom of ALS = 24 months prior to screening. The qualifying first symptoms of ALS are limited to manifestations of weakness in extremity, bulbar, or respiratory muscles. - ALSFRS-R total score = 44 at screening. Patients with a total score of 45 or higher may be rescreened 60±7 days following the original screening date. - Upright FVC = 65.0% of predicted for age, height, sex and ethnicity at screening according to Global Lung Initiative equation - Must be either on riluzole for = 30 days prior to screening or have not taken it for at least 30 days prior to screening - Must have completed at least 2 cycles of edaravone at the time of screening or have not received it for at least 30 days prior to screening - Able to swallow whole tablets Exclusion Criteria: - eGFRCysC < 45.0 mL/min/1.73 m2 at screening - Urine protein/creatinine ratio > 1 mg/mg (113 mg/mmol) at screening - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3-times the upper limit of normal (ULN) - Total bilirubin (TBL), direct or indirect bilirubin above the ULN. - Cognitive impairment, related to ALS or otherwise that impairs the patient's ability to understand and/or comply with study procedures and provide informed consent - Other medically significant neurological conditions that could interfere with the assessment of ALS symptoms, signs or progression. - Has a tracheostomy

Study Design


Intervention

Drug:
Reldesemtiv
Reldesemtiv Oral Tablet
Placebo
Placebo Oral Tablet

Locations

Country Name City State
Australia Flinders Medical Centre Bedford Park South Australia
Australia Brain and Mind Centre Camperdown New South Wales
Australia Concord Repatriation General Hospital Concord New South Wales
Australia Royal Brisbane and Women's Hospital Herston Queensland
Australia The Perron Institute Nedlands Western Australia
Belgium UZ Leuven Gasthuisberg, Department of Neurology Leuven
Canada University of Calgary - Heritage Medical Research Clinic Calgary Alberta
Canada University of Alberta Edmonton Alberta
Canada Stan Cassidy Centre for Rehabilitation Fredericton New Brunswick
Canada McMaster University Medical Centre Hamilton Ontario
Canada London Health Sciences Centre London Ontario
Canada Centre de recherche du CHUM Montréal Quebec
Canada McGill University, Montreal Neurological Institute & Hospital Montréal Quebec
Canada Ottawa Hospital Research Institute - Civic Campus Ottawa Ontario
Canada CHU de Quebec-Université Laval Québec Quebec
Canada Saskatoon City Hospital Saskatoon Saskatchewan
Canada Sunnybrook Research Institute Toronto Ontario
Denmark Deparment of Neurology Bispebjerg University Hospital Copenhagen
France CRC SLA de Lyon Bron
France CHRU de Lille Hopital Roger Salengro Lille
France CHU de Limoges - Hopital Dupuytren Limoges
France CHU de la Timone Marseille
France CHU de Nice - Hôpital Pasteur 2 Nice
France Hopital La Pitie Salpetriere Paris
France CHRU de Tours, Hopital Bretonneau, Clinical Research Center Tours
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Universitatsklinikum Bonn Bonn
Germany Medical School Hannover - Department of Neurology Hanover
Germany Universitatsklinikum Jena Jena
Germany Universitätsklinikum Schleswig Holstein Lübeck
Germany Universitatsklinikum Ulm Ulm
Ireland RSCI Education and Research Centre, Beaumont Hospital Beaumont Dublin
Italy Centro Clinical Nemo - Fondazione Serena Onlus Milan
Italy Ospedale San Luca Milan
Italy Instituti Clinici Scientifici Maugeri Milano
Italy AOU Città della Salute e Scienza (Molinette), Turin
Netherlands UMC Utrecht, Department of Neurology, ALS Center Utrecht
Poland City Clinic Research Warsaw
Portugal Centro Hospitalar Universitario Lisboa Norte, Department of Neurology Lisboa
Spain Hospital Universitari de Bellvitge Barcelona
Spain Hospital Universitario Basurto Bilbao
Spain Hospital San Rafael Madrid
Spain Hospital Universitari i Politecnic La Fe Valencia
Sweden Neurologimottagningen Skane University Hospital Malmö
Sweden Studieenheten Akademiskt Specialistcentrum, Sabbatsberg Hospital Stockholm
Switzerland Muskelzentrum/ALS Clinic Saint Gallen
United Kingdom The Walton Centre NHS Foundation Trust Liverpool
United Kingdom Maurice Wohl Clinical Neuroscience Institute London
United States Michigan Medicine Ann Arbor Michigan
United States University of Colorado Hospital Anschutz Outpatient Pavilion Aurora Colorado
United States Johns Hopkins Outpatient Center Baltimore Maryland
United States Massachusetts General Hospital - Neurological Clinical Research Institute Boston Massachusetts
United States University of Vermont Medical Center Burlington Vermont
United States Atrium Health Neuroscience Institute - Charlotte Charlotte North Carolina
United States Duchossois Center for Advanced Medicine Chicago Illinois
United States Cleveland Clinic Cleveland Ohio
United States Texas Neurology, P.A. Dallas Texas
United States Henry Ford Health System Detroit Michigan
United States VCU Neuroscience Orthopaedic and Wellness Center (NOW) Henrico Virginia
United States Penn State Health Milton S. Hershey Medical Center Hershey Pennsylvania
United States Indiana University Indianapolis Indiana
United States University of Iowa Hospitals and Clinics Iowa City Iowa
United States Mayo Clinic Florida Jacksonville Florida
United States University of Florida Jacksonville Jacksonville Florida
United States The University of Kansas Medical Center Kansas City Kansas
United States Neurology Associates, PC Lincoln Nebraska
United States Cedars-Sinai Medical Center Los Angeles California
United States Froedtert Hospital Milwaukee Wisconsin
United States Vanderbilt University Medical Center - Clinical Research Center Nashville Tennessee
United States Columbia University Medical Center New York New York
United States Hospital for Special Surgery New York New York
United States University of California Irvine - ALS & Neuromuscular Center Orange California
United States Lewis Katz School of Medicine at Temple University Philadelphia Pennsylvania
United States St. Joseph's Hospital & Medical Center - Barrow Neurological Institute Phoenix Arizona
United States Oregon Health and Science University Portland Oregon
United States Providence ALS Center Portland Oregon
United States University of Rochester Medical Center Rochester New York
United States Washington University School of Medicine - Center for Advance Medicine Saint Louis Missouri
United States California Pacific Medical Center - Forbes Norris MDA/ALS Research Center San Francisco California
United States Stanford Hospital and Clinics Stanford California
United States SUNY Upstate Medical University Syracuse New York
United States University of South Florida - Carol and Frank Morsani Center for Advanced Health Care Tampa Florida
United States GW Medical Faculty Associates Washington District of Columbia
United States University of Massachusetts Memorial Medical Center/Medical School Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Cytokinetics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Effect of reldesemtiv versus placebo on functional outcomes in ALS Change from baseline to Week 24 in ALS Functional Rating Scale-Revised (ALSFRS-R) total score; rating scale 0 to 48; higher scores indicate better functional status Baseline to Week 24
Secondary Effect of reldesemtiv versus placebo on combined functional and survival outcomes in ALS Combined assessment of change in ALSFRS-R total score, time to onset of respiratory insufficiency, and survival time up to Week 24. In this joint rank test each individual patient is ranked compared to all other patients based on survival time, time to onset of respiratory insufficiency, and changes from baseline to Week 24 in ALSFRS-R total score. Deaths have the worst rank (with earlier deaths being ranked worse than later deaths); patients with onset of respiratory insufficiency have the next worst rank; and the more favorable changes from baseline at week 24 in ALSFRS-R total score have the best rank using this process. 24 Weeks
Secondary Effect of reldesemtiv versus placebo on ventilatory function Change from baseline to Week 24 in the percent predicted FVC Baseline to Week 24
Secondary Effect of reldesemtiv versus placebo on quality of life Change from baseline to Week 24 in the ALS Assessment Questionnaire-40 (ALSAQ-40) total score; rating scale 0 to 100; higher scores indicate worse quality of life Baseline to Week 24
Secondary Effect of reldesemtiv versus placebo on handgrip strength Change from baseline to Week 24 in handgrip strength (average of both hands) Baseline to Week 24
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