Amyotrophic Lateral SclerosisPhase 3COURAGE-ALSNCT04944784
A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 3 study testing Reldesemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 84 sites in 16 countries.
Trial summary
The purpose of this study is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Reldesemtiv
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 489 participants
- Where
- 84 sitesin 16 countries
- Study dates
- 16 Aug 2021to 18 Jul 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
84 sites in 16 countries.
84 sites in 16 countries
United States36 sites
Michigan Medicine
Ann Arbor, Michigan, 48109
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado, 80045
Johns Hopkins Outpatient Center
Baltimore, Maryland, 21287
Massachusetts General Hospital - Neurological Clinical Research Institute
Boston, Massachusetts, 02114
University of Vermont Medical Center
Burlington, Vermont, 05401
Atrium Health Neuroscience Institute - Charlotte
Charlotte, North Carolina, 28207
Duchossois Center for Advanced Medicine
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
Texas Neurology, P.A.
Dallas, Texas, 75206
Henry Ford Health System
Detroit, Michigan, 48202
VCU Neuroscience Orthopaedic and Wellness Center (NOW)
Henrico, Virginia, 23233
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Indiana University
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Florida Jacksonville
Jacksonville, Florida, 32209
Mayo Clinic Florida
Jacksonville, Florida, 32224
The University of Kansas Medical Center
Kansas City, Kansas, 66160
Neurology Associates, PC
Lincoln, Nebraska, 68506
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center - Clinical Research Center
Nashville, Tennessee, 37232
Hospital for Special Surgery
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
University of California Irvine - ALS & Neuromuscular Center
Orange, California, 92868
Lewis Katz School of Medicine at Temple University
Philadelphia, Pennsylvania, 19140
St. Joseph's Hospital & Medical Center - Barrow Neurological Institute
Phoenix, Arizona, 85013
Providence ALS Center
Portland, Oregon, 97213
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester Medical Center
Rochester, New York, 14642
California Pacific Medical Center - Forbes Norris MDA/ALS Research Center
San Francisco, California, 94109
Washington University School of Medicine - Center for Advance Medicine
St Louis, Missouri, 63108
Stanford Hospital and Clinics
Stanford, California, 94305
SUNY Upstate Medical University
Syracuse, New York, 13210
University of South Florida - Carol and Frank Morsani Center for Advanced Health Care
Tampa, Florida, 33612
GW Medical Faculty Associates
Washington D.C., District of Columbia, 20037
University of Massachusetts Memorial Medical Center/Medical School
Worcester, Massachusetts, 01655
Canada11 sites
University of Calgary - Heritage Medical Research Clinic
Calgary, Alberta, T2N 4Z6
University of Alberta
Edmonton, Alberta, T6G 2B7
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick, E3B 0C7
McMaster University Medical Centre
Hamilton, Ontario, L8N 3Z5
London Health Sciences Centre
London, Ontario, N6A 5A5
Centre de recherche du CHUM
Montreal, Quebec, H2X 0A9
McGill University, Montreal Neurological Institute & Hospital
Montreal, Quebec, H3A 2B4
Ottawa Hospital Research Institute - Civic Campus
Ottawa, Ontario, K1Y 4E9
CHU de Quebec-Université Laval
Québec, Quebec, G1J 1Z4
Saskatoon City Hospital
Saskatoon, Saskatchewan, S7K 0M7
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5
France7 sites
CRC SLA de Lyon
Bron, 69677
CHRU de Lille Hopital Roger Salengro
Lille, 59037
CHU de Limoges - Hopital Dupuytren
Limoges, 87 042
CHU de la Timone
Marseille, 13005
CHU de Nice - Hôpital Pasteur 2
Nice, 06 001
Hopital La Pitie Salpetriere
Paris, 75013
CHRU de Tours, Hopital Bretonneau, Clinical Research Center
Tours, 37044
Germany6 sites
Charité - Universitätsmedizin Berlin
Berlin, 13353
Universitatsklinikum Bonn
Bonn, 53127
Medical School Hannover - Department of Neurology
Hanover, 30625
Universitatsklinikum Jena
Jena, 07747
Universitätsklinikum Schleswig Holstein
Lübeck, 23538
Universitatsklinikum Ulm
Ulm, 89081
Australia5 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Brain and Mind Centre
Camperdown, New South Wales, 2050
Concord Repatriation General Hospital
Concord, New South Wales, 2139
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
The Perron Institute
Nedlands, Western Australia, 6009
Italy4 sites
Ospedale San Luca
Milan, 20149
Centro Clinical Nemo - Fondazione Serena Onlus
Milan, 20162
Instituti Clinici Scientifici Maugeri
Milan, 20138
AOU Città della Salute e Scienza (Molinette),
Turin, 10126
Spain4 sites
Hospital Universitari de Bellvitge
Barcelona, 08907
Hospital Universitario Basurto
Bilbao, 48013
Hospital San Rafael
Madrid, 28016
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Sweden2 sites
Neurologimottagningen Skane University Hospital
Malmö, 21428
Studieenheten Akademiskt Specialistcentrum, Sabbatsberg Hospital
Stockholm, 11361
United Kingdom2 sites
The Walton Centre NHS Foundation Trust
Liverpool, L9 7LJ
Maurice Wohl Clinical Neuroscience Institute
London, SE5 9RX
Denmark1 site
Deparment of Neurology Bispebjerg University Hospital
Copenhagen, 2400
Ireland1 site
RSCI Education and Research Centre, Beaumont Hospital
Beaumont, Dublin, 9
Netherlands1 site
UMC Utrecht, Department of Neurology, ALS Center
Utrecht, 3584 CX
Portugal1 site
Centro Hospitalar Universitario Lisboa Norte, Department of Neurology
Lisbon, 1649-035
About this study
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)
The purpose of this study is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS.
Read the 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
- Being tested
- Reldesemtiv, Placebo
- Keywords
- Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv, COURAGE-ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReldesemtivDrug
Reldesemtiv Oral Tablet
PlaceboDrug
Placebo Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Reldesemtiv |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to Week 24
Secondary outcomes (4)
Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)
Composite Assessment of Function and Survival (CAFS) compares ranked outcomes based on change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score (0-48; higher scores indicate better function), time in months to dependence on assisted ventilation (DOAV) and time in months to death. Deceased participants are ranked by time-to-death; earliest deaths ranked the lowest. DOAV survivors are ranked more favorably than those who have died but lower than those alive and not DOAV. Non-DOAV survivors are ranked based on change in ALSFRS-R (largest decline in ALSFRS-R ranked lower than less decline or improvement in ALSFRS-R). Unitless ranked scores range from 1-482 (Full Analysis Set) with larger rank scores associated with a better outcome. Ranks were analyzed using stratified Wilcoxon test comparing the ranked scores between reldesemtiv and placebo, adjusting for baseline riluzole and edaravone use. The win probability and the ratio (reldesemtiv vs placebo) are presented.
Measured: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Ventilatory Function
Change from baseline in percent predicted forced vital capacity (FVC) using an in-clinic spirometer; a negative number for change from baseline indicates respiratory function decline relative to baseline
Measured: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Quality of Life
Change from baseline in ALSAQ-40 total score. ALSAQ-40 = Amyotrophic Lateral Sclerosis Assessment Questionnaire; summary scores range from 0 (best health status) to 100 (worst health status); ALSAQ-40 total score is calculated as the sum of the summary scores from the 5 domains; lower score corresponds to better health-related quality of life.
Measured: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Handgrip Strength
Change from baseline in maximum handgrip strength (average of both hands) measured bilaterally by an electronic hand dynamometer
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start16 Aug 2021
- Primary completion18 Jul 2023
- Study completion18 Jul 2023
Why it stopped: The DMC recommended the trial be discontinued due to futility following a planned second interim analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 489 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cytokinetics, MD, Study director, Cytokinetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04944784
- Sponsor's protocol ID
- CY 5031
- Other IDs
- 2020-004040-29
- Acronym
- COURAGE-ALS
- Status last verified
- Nov 2024
- First submitted
- 16 Jun 2021
- Last updated
- 5 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 Apr;73(4):608-614. doi: 10.1002/mus.70150. Epub 2026 Jan 19.
PubMed 41553108Rudnicki 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.
PubMed 40576049Rudnicki SA, Al-Chalabi A, Andrews JA, Chio A, Corcia P, Couratier P, Cudkowicz ME, De Carvalho M, Genge A, Hardiman O, 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, Herder KE, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Shefner JM; Courage-Als study group. Hospitalizations as an outcome measure in COURAGE-ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2025 Nov;26(7-8):802-811. doi: 10.1080/21678421.2025.2515907. Epub 2025 Jun 12.
PubMed 40503807Shefner 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.
PubMed 40126464Shefner 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.
PubMed 37254449
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04944784
- Acronym / sponsor ID
- COURAGE-ALS / CY 5031
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic Lateral Sclerosis, ALS, CK-2127107, Reldesemtiv, COURAGE-ALS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The DMC recommended the trial be discontinued due to futility following a planned second interim analysis.
- Enrolment
- 489 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- 16 Aug 2021 (actual)
- Primary completion
- 18 Jul 2023 (actual)
- Study completion
- 18 Jul 2023 (actual)
- First posted
- 30 Jun 2021 (actual)
- Results
- Posted 5 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Reldesemtiv Group, Double-Blind Period | Experimental | Drug: ReldesemtivParticipants 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. |
| Placebo Group, Double-Blind Period | Placebo comparator | Drug: PlaceboParticipants in this arm take 2 placebo oral tablets twice a day from Day 1 until Week 24. |
| Delayed Start Group, Active Drug Period | Experimental | Drug: ReldesemtivParticipants 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. |
| Early Start Group, Active Drug Period | Experimental | Drug: ReldesemtivParticipants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ReldesemtivReldesemtiv Oral Tablet | Drug | Delayed Start Group, Active Drug Period, Early Start Group, Active Drug Period, Reldesemtiv Group, Double-Blind Period |
| PlaceboPlacebo Oral Tablet | Drug | Placebo Group, Double-Blind Period |
Primary outcome
Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)
Time frame: Baseline to Week 24
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
4 secondary outcomes
Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Ventilatory Function
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Quality of Life
Time frame: Baseline to Week 24
Effect of Reldesemtiv Versus Placebo on Handgrip Strength
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41553108Rudnicki 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 Apr;73(4):608-614. doi: 10.1002/mus.70150. Epub 2026 Jan 19.
- Derived from this study: PubMed 40576049Rudnicki 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.
- Derived from this study: PubMed 40503807Rudnicki SA, Al-Chalabi A, Andrews JA, Chio A, Corcia P, Couratier P, Cudkowicz ME, De Carvalho M, Genge A, Hardiman O, 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, Herder KE, Kupfer S, Malik FI, Meng L, Simkins TJ, Wei J, Wolff AA, Shefner JM; Courage-Als study group. Hospitalizations as an outcome measure in COURAGE-ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2025 Nov;26(7-8):802-811. doi: 10.1080/21678421.2025.2515907. Epub 2025 Jun 12.
- Derived from this study: PubMed 40126464Shefner 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.
- Derived from this study: PubMed 37254449Shefner 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cytokinetics, MD study director
Cytokinetics
84 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Reldesemtiv in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 84 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in United States, Canada, France, Germany, Australia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04944784, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.