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

NCT04944784 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CY 50312020-004040-29
• Study Type: interventional
• Target: 489
• Locations: 16 countries
• Sites: 84

Brief Summary

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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)

  Change from baseline to Week 24 in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score using MMRM without multiple imputation; rating scale 0 to 48; higher scores indicate better functional status

  Baseline to Week 24

Secondary Outcomes (4)

• Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)

  Baseline to Week 24

• Effect of Reldesemtiv Versus Placebo on Ventilatory Function

  Baseline to Week 24

• Effect of Reldesemtiv Versus Placebo on Quality of Life

  Baseline to Week 24

• Effect of Reldesemtiv Versus Placebo on Handgrip Strength

  Baseline to Week 24

Study Arms (4)

Reldesemtiv Group, Double-Blind Period

EXPERIMENTAL

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.

Drug: Reldesemtiv

Placebo Group, Double-Blind Period

PLACEBO COMPARATOR

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

Drug: Placebo

Delayed Start Group, Active Drug Period

EXPERIMENTAL

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.

Drug: Reldesemtiv

Early Start Group, Active Drug Period

EXPERIMENTAL

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.

Drug: Reldesemtiv

Interventions

Reldesemtiv DRUG

Reldesemtiv Oral Tablet

Delayed Start Group, Active Drug Period; Early Start Group, Active Drug Period; Reldesemtiv Group, Double-Blind Period

Placebo DRUG

Placebo Oral Tablet

Placebo Group, Double-Blind Period

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (84)

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

Phoenix, Arizona, 85013, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Irvine - ALS & Neuromuscular Center

Orange, California, 92868, United States

Location

California Pacific Medical Center - Forbes Norris MDA/ALS Research Center

San Francisco, California, 94109, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Colorado Hospital Anschutz Outpatient Pavilion

Aurora, Colorado, 80045, United States

Location

GW Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

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

Tampa, Florida, 33612, United States

Location

Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins Outpatient Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital - Neurological Clinical Research Institute

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Memorial Medical Center/Medical School

Worcester, Massachusetts, 01655, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine - Center for Advance Medicine

St Louis, Missouri, 63108, United States

Location

Neurology Associates, PC

Lincoln, Nebraska, 68506, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Atrium Health Neuroscience Institute - Charlotte

Charlotte, North Carolina, 28207, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence ALS Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Lewis Katz School of Medicine at Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Vanderbilt University Medical Center - Clinical Research Center

Nashville, Tennessee, 37232, United States

Location

Texas Neurology, P.A.

Dallas, Texas, 75206, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

VCU Neuroscience Orthopaedic and Wellness Center (NOW)

Henrico, Virginia, 23233, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Brain and Mind Centre

Camperdown, New South Wales, 2050, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

The Perron Institute

Nedlands, Western Australia, 6009, Australia

Location

UZ Leuven Gasthuisberg, Department of Neurology

Leuven, 3000, Belgium

Location

University of Calgary - Heritage Medical Research Clinic

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, E3B 0C7, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Ottawa Hospital Research Institute - Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Centre de recherche du CHUM

Montreal, Quebec, H2X 0A9, Canada

Location

McGill University, Montreal Neurological Institute & Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

CHU de Quebec-Université Laval

Québec, Quebec, G1J 1Z4, Canada

Location

Saskatoon City Hospital

Saskatoon, Saskatchewan, S7K 0M7, Canada

Location

Deparment of Neurology Bispebjerg University Hospital

Copenhagen, 2400, Denmark

Location

CRC SLA de Lyon

Bron, 69677, France

Location

CHRU de Lille Hopital Roger Salengro

Lille, 59037, France

Location

CHU de Limoges - Hopital Dupuytren

Limoges, 87 042, France

Location

CHU de la Timone

Marseille, 13005, France

Location

CHU de Nice - Hôpital Pasteur 2

Nice, 06 001, France

Location

Hopital La Pitie Salpetriere

Paris, 75013, France

Location

CHRU de Tours, Hopital Bretonneau, Clinical Research Center

Tours, 37044, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitatsklinikum Bonn

Bonn, 53127, Germany

Location

Medical School Hannover - Department of Neurology

Hanover, 30625, Germany

Location

Universitatsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Schleswig Holstein

Lübeck, 23538, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

RSCI Education and Research Centre, Beaumont Hospital

Beaumont, Dublin, 9, Ireland

Location

Ospedale San Luca

Milan, 20149, Italy

Location

Centro Clinical Nemo - Fondazione Serena Onlus

Milan, 20162, Italy

Location

Instituti Clinici Scientifici Maugeri

Milan, 20138, Italy

Location

AOU Città della Salute e Scienza (Molinette),

Turin, 10126, Italy

Location

UMC Utrecht, Department of Neurology, ALS Center

Utrecht, 3584 CX, Netherlands

Location

City Clinic Research

Warsaw, 02-473, Poland

Location

Centro Hospitalar Universitario Lisboa Norte, Department of Neurology

Lisbon, 1649-035, Portugal

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario Basurto

Bilbao, 48013, Spain

Location

Hospital San Rafael

Madrid, 28016, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Neurologimottagningen Skane University Hospital

Malmo, 21428, Sweden

Location

Studieenheten Akademiskt Specialistcentrum, Sabbatsberg Hospital

Stockholm, 11361, Sweden

Location

Muskelzentrum/ALS Clinic

Sankt Gallen, 9007, Switzerland

Location

The Walton Centre NHS Foundation Trust

Liverpool, L9 7LJ, United Kingdom

Location

Maurice Wohl Clinical Neuroscience Institute

London, SE5 9RX, United Kingdom

Location

Related Publications (4)

• Rudnicki SA, Giacomelli E, Herder K, Ingre C, Kupfer S, Malik FI, Meng L, Paganoni S, Schellenberg K, Scirocco E, Simkins T, Wei J, Shefner JM; COURAGE-ALS Study Group. The Use of Durable Medical Equipment in COURAGE-ALS, a Phase 3, Multicentre, Randomized Clinical Trial for ALS. Muscle Nerve. 2026 Jan 19. doi: 10.1002/mus.70150. Online ahead of print.

  PMID: 41553108 DERIVED

• 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 Nov;26(7-8):812-820. doi: 10.1080/21678421.2025.2523941. Epub 2025 Jun 27.

  PMID: 40576049 DERIVED

• 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.

  PMID: 40126464 DERIVED

• 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.

  PMID: 37254449 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

reldesemtiv

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

The Data Monitoring Committee reviewed unblinded data at the second planned interim analysis and recommended discontinuation of the clinical trial due to futility.

Results Point of Contact

• Title: Cytokinetics MD
• Organization: Cytokinetics

medicalaffairs@cytokinetics.com

6506242929

Study Officials

• Cytokinetics, MD

  Cytokinetics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 30, 2021
• Study Start: August 16, 2021
• Primary Completion: July 18, 2023
• Study Completion: July 18, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); CA (11); IT (4); CH (1); PT (1); DK (1); US (36); FR (7); AU (5); DE (6); ES (4); SE (2); GB (2); IE (1); NL (1); PL (1)