A Phase 2, Multi-Center, Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 458
- 试验地点
- 63
- 主要终点
- Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)
研究概览
简要总结
The purpose of this study was to assess the effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS.
详细描述
This was a double-blind, randomized, placebo-controlled, dose ranging study of reldesemtiv in patients with ALS. Eligible patients were randomized (1:1:1:1) to receive placebo or one of three doses of reldesemtiv (150, 300, or 450 mg twice daily) for 12 weeks. Randomization was stratified by riluzole concomitant use/non-use and edaravone concomitant use/non-use. Concomitant riluzole and edaravone were allowed as long as the riluzole dose had been stable for at least 30 days prior to screening and edaravone had been taken for 2 cycles prior to screening; these drugs could not be initiated during the study.
A total of 7 study visits were planned: screening, Day 1 (first dosing day), Weeks 2, 4, 8, and 12, and follow-up (4 weeks after the last dose of study drug). Study drug (placebo or reldesemtiv) was to be taken twice daily, approximately 12 hours (± 2 hours) apart and within 2 hours following a meal.
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
- •Diagnosis of familial or sporadic ALS ≤ 24 months prior to screening
- •Upright Slow Vital Capacity (SVC) ≥ 60% of predicted for age, height and sex at screening
- •Able to swallow tablets
- •A caregiver (if one is needed)
- •Able to perform reproducible pulmonary function tests
- •Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
- •Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug until 10 weeks after the last dose to either use acceptable methods of contraception or abstain from sex
- •Female patients must be post-menopausal or sterilized or must not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the study and use acceptable methods of contraception or abstain from heterosexual intercourse from Screening until 10 weeks after last dose of study drug
- •Patients must be either on riluzole for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and not planning to start riluzole during the course of the study.
- •Patients on edaravone must have completed at least 2 cycles of dosing with edaravone at the time of screening or have not taken edaravone for at least 30 days prior to screening and not planning to start edaravone during the course of the study.
排除标准
- •At the time of screening, any use of non-invasive ventilation (NIV), e.g. continuous positive airway pressure [CPAP], noninvasive bi-level positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
- •Neurological impairment due to a condition other than ALS
- •Presence at screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data
- •Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
- •Known to have received CK-2127107 or tirasemtiv in any previous clinical trial
- •Has received or is considering receiving during the course of the study any form of stem cell therapy for the treatment of ALS
- •Has received or is considering receiving during the course of the study any form of gene therapy for the treatment of ALS
- •Has received or is considering obtaining during the course of the study a diaphragmatic pacing system
- •History of substance abuse within the past 2 years
- •Use of certain medications
研究组 & 干预措施
Reldesemtiv 150 mg twice daily
Patients in this arm took 1 reldesemtiv 150 mg oral tablet and 2 matching placebo tablets every 12 hours for 12 weeks.
干预措施: Reldesemtiv (Drug)
Reldesemtiv 300 mg twice daily
Patients in this arm took 2 reldesemtiv 150 mg oral tablets and 1 matching placebo tablet every 12 hours for 12 weeks.
干预措施: Reldesemtiv (Drug)
Reldesemtiv 450 mg twice daily
Patients in this arm took 3 reldesemtiv 150 mg oral tablets every 12 hours for 12 weeks.
干预措施: Reldesemtiv (Drug)
Placebo
Patients in this arm took 3 placebo oral tablets every 12 hours for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)
时间窗: Baseline to Week 12
Slow vital capacity was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to percent predicted values using the Global Lung Initiative equation (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\]).
次要结局
- Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score(Baseline to Week 12)
- Slope of Muscle Strength Mega-score From Baseline to Week 12(Baseline to Week 12)