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)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 489
- 试验地点
- 84
- 主要终点
- Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)
研究概览
简要总结
The purpose of this study is to assess the effect of reldesemtiv versus placebo on functional outcomes in ALS.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Reldesemtiv (Drug)
Placebo Group, Double-Blind Period
Participants in this arm take 2 placebo oral tablets twice a day from Day 1 until Week 24.
干预措施: Placebo (Drug)
Delayed Start Group, Active Drug Period
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.
干预措施: Reldesemtiv (Drug)
Early Start Group, Active Drug Period
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.
干预措施: Reldesemtiv (Drug)
结局指标
主要结局
Effect of Reldesemtiv Versus Placebo on Functional Outcomes in Amyotrophic Lateral Sclerosis (ALS)
时间窗: 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
次要结局
- 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)