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) (COURAGE-ALS)

Study Purpose:

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

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase III

Study Chair(s)/Principal Investigator(s):

Clinicaltrials.gov ID (11 digit #):

NCT04944784

Neals Affiliated?

Yes

Coordinating Center Contact Information


Cytokinetics, MD / .(JavaScript must be enabled to view this email address) / 650-624-2929
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

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

Study Sponsor:

Cytokinetics

Participant Duration:

Estimated Enrollment:

555

Estimated Study Start Date:

08/16/2021

Estimated Study Completion Date:

03/31/2024

Posting Last Modified Date:

11/02/2021

Date Study Added to alsconsortium.org:

11/02/2021
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    80

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    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

  • Site Contact Information

    Barrow Neurological Institute
    Phoenix, Arizona 85013
    United States

    University of California Irvine
    Orange, California 92868
    United States

    California Pacific Medical Center
    San Francisco, California 94109
    United States

    Stanford Hospital and Clinics
    Stanford, California 94305
    United States

    University of Colorado Hospital Anschutz Outpatient Pavilion
    Aurora, Colorado 80045
    United States

    GW Medical Faculty Associates
    Washington, District of Columbia 20037
    United States

    Mayo Clinic Florida
    Jacksonville, Florida 32224
    United States

    University of Florida Jacksonville
    Jacksonville, Florida 32209
    United States

    University of South Florida
    Tampa, Florida 33612
    United States

    Duchossois Center for Advanced Medicine
    Chicago, Illinois 60637
    United States

    The University of Kansas Medical Center
    Kansas City, Kansas 66160
    United States

    Johns Hopkins Outpatient Center
    Baltimore, Maryland 21287
    United States

    Henry Ford Health System
    Detroit, Michigan 48202
    United States

    Washington University School of Medicine
    Saint Louis, Missouri 63108
    United States

    Neurology Associates, PC
    Lincoln, Nebraska 68506
    United States

    Columbia University Medical Center
    New York, New York 10032
    United States

    Hospital for Special Surgery
    New York, New York 10021
    United States

    SUNY Upstate Medical University
    Syracuse, New York 13210
    United States

    Atrium Health Neuroscience Institute - Charlotte
    Charlotte, North Carolina 28207
    United States

    Cleveland Clinic
    Cleveland, Ohio 44195
    United States

    Texas Neurology, P.A.
    Dallas, Texas 75206
    United States

    University of Vermont Medical Center
    Burlington, Vermont 05401
    United States

    VCU Neuroscience Orthopaedic and Wellness Center (NOW)
    Henrico, Virginia 23233
    United States

    Froedtert Hospital
    Milwaukee, Wisconsin 53226
    United States

    The Perron Institute
    Nedlands,
    Australia

    University of Calgary
    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

    Ottawa Hospital Research Institute
    Ottawa, Ontario
    Canada

    Sunnybrook Research Institute
    Toronto, Ontario
    Canada

    Centre de recherche du CHUM
    Montréal, Quebec
    Canada

    McGill University, Montreal Neurological Institute & Hospital
    Montréal, Quebec
    Canada

    CHU de Quebec-Université Laval
    Québec, Quebec
    Canada

    Saskatoon City Hospital
    Saskatoon, Saskatchewan
    Canada