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

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)

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04944784

Acronym

COURAGE-ALS

Enrollment

489

Registered

2021-06-30

Start date

2021-08-16

Completion date

2023-07-18

Last updated

2024-12-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Amyotrophic Lateral Sclerosis

Keywords

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

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

Interventions

DRUGReldesemtiv

Reldesemtiv Oral Tablet

DRUGPlacebo

Placebo Oral Tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)	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

Secondary

Measure	Time frame	Description
Effect of Reldesemtiv Versus Placebo on Combined Functional and Survival Outcomes in Amyotrophic Lateral Sclerosis (ALS)	Baseline to Week 24	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.
Effect of Reldesemtiv Versus Placebo on Ventilatory Function	Baseline to Week 24	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
Effect of Reldesemtiv Versus Placebo on Quality of Life	Baseline to Week 24	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.
Effect of Reldesemtiv Versus Placebo on Handgrip Strength	Baseline to Week 24	Change from baseline in maximum handgrip strength (average of both hands) measured bilaterally by an electronic hand dynamometer

Countries

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

Participant flow

Pre-assignment details

Three participants were randomized but never dosed in the study.

Participants by arm

Arm	Count
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. Reldesemtiv: Reldesemtiv Oral Tablet	325
Placebo Group, Double-Blind Period Participants in this arm take 2 placebo oral tablets twice a day from Day 1 until Week 24. Placebo: Placebo Oral Tablet	161
Total	486

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Active Drug Period	Adverse Event	0	0	3	6
Active Drug Period	Death	0	0	3	4
Active Drug Period	Lack of Efficacy	0	0	2	2
Active Drug Period	Lost to Follow-up	0	0	0	1
Active Drug Period	Participant Choice	0	0	0	1
Active Drug Period	Planned Medical Assistance in Dying	0	0	0	1
Active Drug Period	Progressive Disease	0	0	4	4
Active Drug Period	Study Terminated by Sponsor	0	0	49	92
Active Drug Period	Withdrawal by Subject	0	0	4	7
Double-blind Period	Adverse Event	20	4	0	0
Double-blind Period	Death	7	2	0	0
Double-blind Period	Lack of Efficacy	0	1	0	0
Double-blind Period	Participant Choice	1	1	0	0
Double-blind Period	Physician Decision	2	1	0	0
Double-blind Period	Planned Medical Assistance in Dying	0	3	0	0
Double-blind Period	Progressive Disease	2	2	0	0
Double-blind Period	Sponsor Request	2	1	0	0
Double-blind Period	Study Terminated by Sponsor	96	46	0	0
Double-blind Period	Withdrawal by Subject	15	4	0	0

Baseline characteristics

Characteristic	Placebo Group, Double-Blind Period	Total	Reldesemtiv Group, Double-Blind Period
Age, Continuous	59.8 years STANDARD_DEVIATION 10.79	59.4 years STANDARD_DEVIATION 10.92	59.2 years STANDARD_DEVIATION 11
ALSAQ-40 Total Score	31.6 score on a scale STANDARD_DEVIATION 16.8	29.9 score on a scale STANDARD_DEVIATION 16	29.1 score on a scale STANDARD_DEVIATION 15.56
ALSFRS-R total score	36.6 score on a scale STANDARD_DEVIATION 5.44	37.0 score on a scale STANDARD_DEVIATION 5.14	37.2 score on a scale STANDARD_DEVIATION 4.97
Average Maximum Handgrip Strength	38.28 pounds STANDARD_DEVIATION 26.439	39.58 pounds STANDARD_DEVIATION 26.216	40.22 pounds STANDARD_DEVIATION 26.122
Body Mass Index	26.4 kg/m^2 STANDARD_DEVIATION 4.41	26.8 kg/m^2 STANDARD_DEVIATION 5.29	26.9 kg/m^2 STANDARD_DEVIATION 5.67
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants	27 Participants	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	132 Participants	410 Participants	278 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants	49 Participants	32 Participants
Forced vital capacity (FVC) percent predicted	85.8 percent predicted STANDARD_DEVIATION 14.19	84.9 percent predicted STANDARD_DEVIATION 14.53	84.5 percent predicted STANDARD_DEVIATION 14.69
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	3 Participants	9 Participants	6 Participants
Race (NIH/OMB) Black or African American	4 Participants	5 Participants	1 Participants
Race (NIH/OMB) More than one race	5 Participants	14 Participants	9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	149 Participants	457 Participants	308 Participants
Region of Enrollment Australia	5 Participants	27 Participants	22 Participants
Region of Enrollment Belgium	1 Participants	7 Participants	6 Participants
Region of Enrollment Canada	24 Participants	72 Participants	48 Participants
Region of Enrollment Denmark	0 Participants	1 Participants	1 Participants
Region of Enrollment France	14 Participants	38 Participants	24 Participants
Region of Enrollment Germany	11 Participants	46 Participants	35 Participants
Region of Enrollment Ireland	2 Participants	8 Participants	6 Participants
Region of Enrollment Italy	11 Participants	32 Participants	21 Participants
Region of Enrollment Netherlands	7 Participants	12 Participants	5 Participants
Region of Enrollment Poland	7 Participants	16 Participants	9 Participants
Region of Enrollment Portugal	3 Participants	15 Participants	12 Participants
Region of Enrollment Spain	10 Participants	39 Participants	29 Participants
Region of Enrollment Sweden	7 Participants	15 Participants	8 Participants
Region of Enrollment Switzerland	0 Participants	2 Participants	2 Participants
Region of Enrollment United Kingdom	3 Participants	3 Participants	0 Participants
Region of Enrollment United States	56 Participants	153 Participants	97 Participants
Sex: Female, Male Female	64 Participants	177 Participants	113 Participants
Sex: Female, Male Male	97 Participants	309 Participants	212 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	9 / 325	6 / 161	5 / 96	8 / 180
other Total, other adverse events	258 / 325	125 / 161	65 / 96	122 / 180
serious Total, serious adverse events	41 / 325	25 / 161	14 / 96	33 / 180

Arm	Measure	Value (MEAN)	Dispersion
Reldesemtiv Group, Double-Blind Period	Effect of Reldesemtiv Versus Placebo on Ventilatory Function	-10.562 percent predicted	Standard Deviation 12.8178
Placebo Group, Double-Blind Period	Effect of Reldesemtiv Versus Placebo on Ventilatory Function	-9.677 percent predicted	Standard Deviation 13.1073

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026