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

NCT ID: NCT04944784

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 489 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-16
• Study Completion Date: 2023-07-18

Brief Summary

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

Detailed 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 21 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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; ALS; CK-2127107; Reldesemtiv; COURAGE-ALS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Reldesemtiv Group, Double-Blind Period

Participants in this arm take 2 reldesemtiv 150 mg oral tablets twice a day for a 600 mg total daily dose from Day 1 until Week 24.

Group Type: EXPERIMENTAL

Reldesemtiv

Intervention Type: DRUG

Reldesemtiv Oral Tablet

Placebo Group, Double-Blind Period

Participants in this arm take 2 placebo oral tablets twice a day from Day 1 until Week 24.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Oral Tablet

Delayed Start Group, Active Drug Period

Participants in this arm were those who received placebo in the double-blind period and reldesemtiv in the active drug period. Participants take 2 reldesemtiv 150 mg oral tablets twice a day for a 600 mg total daily dose from Week 24 until Week 48. Patients who were down-titrated for any reason during the 24 weeks of blinded dosing take 1 reldesemtiv 150 mg oral tablet twice a day for a 300 mg total daily dose from Week 24 until Week 48.

Group Type: EXPERIMENTAL

Reldesemtiv

Intervention Type: DRUG

Reldesemtiv Oral Tablet

Early Start Group, Active Drug Period

Participants in this arm were those who received reldesemtiv in the double-blind and active drug periods. Participants take 2 reldesemtiv 150 mg oral tablets twice a day for a 600 mg total daily dose from Week 24 until Week 48. Patients who were down-titrated for any reason during the 24 weeks of blinded dosing take 1 reldesemtiv 150 mg oral tablet twice a day for a 300 mg total daily dose from Week 24 until Week 48.

Group Type: EXPERIMENTAL

Reldesemtiv

Intervention Type: DRUG

Reldesemtiv Oral Tablet

Interventions

Reldesemtiv

Reldesemtiv Oral Tablet

Intervention Type: DRUG

Placebo

Placebo Oral Tablet

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cytokinetics, MD

Role: STUDY_DIRECTOR

Cytokinetics

Locations

St. Joseph's Hospital & Medical Center - Barrow Neurological Institute

Phoenix, Arizona, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California Irvine - ALS & Neuromuscular Center

Orange, California, 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

University of Colorado Hospital Anschutz Outpatient Pavilion

Aurora, Colorado, United States

GW Medical Faculty Associates

Washington D.C., District of Columbia, United States

University of Florida Jacksonville

Jacksonville, Florida, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of South Florida - Carol and Frank Morsani Center for Advanced Health Care

Tampa, Florida, United States

Duchossois Center for Advanced Medicine

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

The University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins Outpatient Center

Baltimore, Maryland, United States

Massachusetts General Hospital - Neurological Clinical Research Institute

Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center/Medical School

Worcester, Massachusetts, United States

Michigan Medicine

Ann Arbor, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Washington University School of Medicine - Center for Advance Medicine

St Louis, Missouri, United States

Neurology Associates, PC

Lincoln, Nebraska, United States

Hospital for Special Surgery

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Atrium Health Neuroscience Institute - Charlotte

Charlotte, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Providence ALS Center

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center - Clinical Research Center

Nashville, Tennessee, United States

Texas Neurology, P.A.

Dallas, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

VCU Neuroscience Orthopaedic and Wellness Center (NOW)

Henrico, Virginia, United States

Froedtert Hospital

Milwaukee, Wisconsin, United States

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

Flinders Medical Centre

Bedford Park, South Australia, Australia

The Perron Institute

Nedlands, Western Australia, Australia

UZ Leuven Gasthuisberg, Department of Neurology

Leuven, , Belgium

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

Ottawa Hospital Research Institute - Civic Campus

Ottawa, Ontario, Canada

Sunnybrook Research Institute

Toronto, Ontario, Canada

Centre de recherche du CHUM

Montreal, Quebec, Canada

McGill University, Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

CHU de Quebec-Université Laval

Québec, Quebec, Canada

Saskatoon City Hospital

Saskatoon, Saskatchewan, Canada

Deparment of Neurology Bispebjerg University Hospital

Copenhagen, , Denmark

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, , France

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, , Germany

RSCI Education and Research Centre, Beaumont Hospital

Beaumont, Dublin, Ireland

Ospedale San Luca

Milan, , Italy

Centro Clinical Nemo - Fondazione Serena Onlus

Milan, , Italy

Instituti Clinici Scientifici Maugeri

Milan, , Italy

AOU Città della Salute e Scienza (Molinette),

Turin, , Italy

UMC Utrecht, Department of Neurology, ALS Center

Utrecht, , Netherlands

City Clinic Research

Warsaw, , Poland

Centro Hospitalar Universitario Lisboa Norte, Department of Neurology

Lisbon, , Portugal

Hospital Universitari de Bellvitge

Barcelona, , Spain

Hospital Universitario Basurto

Bilbao, , Spain

Hospital San Rafael

Madrid, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Neurologimottagningen Skane University Hospital

Malmo, , Sweden

Studieenheten Akademiskt Specialistcentrum, Sabbatsberg Hospital

Stockholm, , Sweden

Muskelzentrum/ALS Clinic

Sankt Gallen, , Switzerland

The Walton Centre NHS Foundation Trust

Liverpool, , United Kingdom

Maurice Wohl Clinical Neuroscience Institute

London, , United Kingdom

Countries

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

References

Rudnicki SA, Gebrehiwet P, Kupfer S, Malik FI, Meng L, Simkins T, Wei J, Wolff AA, Shefner JM. Participant, site personnel and sponsor perspectives on decentralized trial features in COURAGE-ALS: a randomized clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2025 Jun 27:1-9. doi: 10.1080/21678421.2025.2523941. Online ahead of print.

Reference Type: DERIVED

PMID: 40576049 (View on PubMed)

Shefner JM, Cudkowicz ME, Genge A, Hardiman O, Al-Chalabi A, Andrews JA, Chio A, Corcia P, Couratier P, de Carvalho M, Heiman-Patterson T, Henderson RD, Ingre C, Johnston W, Ludolph A, Maragakis NJ, Miller TM, Mora JS, Petri S, Simmons Z, van den Berg LH, Zinman L, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Rudnicki SA; COURAGE-ALS Study Group. Reldesemtiv in Amyotrophic Lateral Sclerosis: Results From the COURAGE-ALS Randomized Clinical Trial. JAMA Neurol. 2025 May 1;82(5):477-485. doi: 10.1001/jamaneurol.2025.0241.

Reference Type: DERIVED

PMID: 40126464 (View on PubMed)

Shefner JM, Al-Chalabi A, Andrews JA, Chio A, De Carvalho M, Cockroft BM, Corcia P, Couratier P, Cudkowicz ME, Genge A, Hardiman O, Heiman-Patterson T, Henderson RD, Ingre C, Jackson CE, Johnston W, Lechtzin N, Ludolph A, Maragakis NJ, Miller TM, Mora Pardina JS, Petri S, Simmons Z, Van Den Berg LH, Zinman L, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Rudnicki SA. COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success. Amyotroph Lateral Scler Frontotemporal Degener. 2023 Aug;24(5-6):523-534. doi: 10.1080/21678421.2023.2216223. Epub 2023 May 30.

Reference Type: DERIVED

PMID: 37254449 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004040-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CY 5031

Identifier Type: -

Identifier Source: org_study_id