A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis Clinical Trial

— COURAGE-ALS  

Official title:

A Phase 3, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)

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
• Start date: August 16, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2023
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• 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: March 31, 2023
• Est. primary completion date: March 31, 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

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