Clinical trial NCT04944784: A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
ALS
CK-2127107
Reldesemtiv
COURAGE-ALS
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 489
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)
timeFrame: Baseline to Week 24
measure: Effect of Reldesemtiv Versus Placebo on Ventilatory Function
timeFrame: Baseline to Week 24
measure: Effect of Reldesemtiv Versus Placebo on Quality of Life
timeFrame: Baseline to Week 24
measure: Effect of Reldesemtiv Versus Placebo on Handgrip Strength
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine - ALS & Neuromuscular Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion
state: Colorado
city: Washington
country: United States
facility: GW Medical Faculty Associates
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
state: Florida
city: Chicago
country: United States
facility: Duchossois Center for Advanced Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital - Neurological Clinical Research Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center/Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Center for Advance Medicine
state: Missouri
city: Lincoln
country: United States
facility: Neurology Associates, PC
state: Nebraska
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Atrium Health Neuroscience Institute - Charlotte
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence ALS Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Lewis Katz School of Medicine at Temple University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Clinical Research Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology, P.A.
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Henrico
country: United States
facility: VCU Neuroscience Orthopaedic and Wellness Center (NOW)
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Camperdown
country: Australia
facility: Brain and Mind Centre
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Nedlands
country: Australia
facility: The Perron Institute
state: Western Australia
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg, Department of Neurology
city: Calgary
country: Canada
facility: University of Calgary - Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Fredericton
country: Canada
facility: Stan Cassidy Centre for Rehabilitation
state: New Brunswick
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute - Civic Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montréal
country: Canada
facility: Centre de recherche du CHUM
state: Quebec
city: Montréal
country: Canada
facility: McGill University, Montreal Neurological Institute & Hospital
state: Quebec
city: Québec
country: Canada
facility: CHU de Quebec-Université Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital
state: Saskatchewan
city: Copenhagen
country: Denmark
facility: Deparment of Neurology Bispebjerg University Hospital
city: Bron
country: France
facility: CRC SLA de Lyon
city: Lille
country: France
facility: CHRU de Lille Hopital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hopital Dupuytren
city: Marseille
country: France
facility: CHU de la Timone
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur 2
city: Paris
country: France
facility: Hopital La Pitie Salpetriere
city: Tours
country: France
facility: CHRU de Tours, Hopital Bretonneau, Clinical Research Center
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Hanover
country: Germany
facility: Medical School Hannover - Department of Neurology
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig Holstein
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Beaumont
country: Ireland
facility: RSCI Education and Research Centre, Beaumont Hospital
state: Dublin
city: Milano
country: Italy
facility: Instituti Clinici Scientifici Maugeri
city: Milan
country: Italy
facility: Ospedale San Luca
city: Milan
country: Italy
facility: Centro Clinical Nemo - Fondazione Serena Onlus
city: Turin
country: Italy
facility: AOU Città della Salute e Scienza (Molinette),
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Department of Neurology, ALS Center
city: Warsaw
country: Poland
facility: City Clinic Research
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte, Department of Neurology
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto
city: Madrid
country: Spain
facility: Hospital San Rafael
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Malmö
country: Sweden
facility: Neurologimottagningen Skane University Hospital
city: Stockholm
country: Sweden
facility: Studieenheten Akademiskt Specialistcentrum, Sabbatsberg Hospital
city: Saint Gallen
country: Switzerland
facility: Muskelzentrum/ALS Clinic
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Maurice Wohl Clinical Neuroscience Institute
Study officials:
affiliation: Cytokinetics
name: Cytokinetics, MD
role: STUDY_DIRECTOR
References: