A Randomized Double-blind Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults with Symptomatic Non-obstructive Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 420
- 试验地点
- 5
- 主要终点
- 1) To assess the efficacy of a 48-week course of
研究概览
简要总结
CV027031 is a Phase 3, double-blind, randomized, placebo-controlled, multicenter, international, parallel-group study to evaluate the safety, tolerability, and efficacy of mavacamten compared with placebo in participants with symptomatic nHCM. The study will randomize approximately 420 participants at 180 sites in a 1:1 ratio to mavacamten and placebo. Double-blind treatment with oral mavacamten or placebo may range from a minimum of 48 weeks for the last participant randomized to a maximum of 120 weeks for the first participant randomized. At Week 48 after study intervention, the effects of mavacamten compared to placebo on health status (symptoms and physical limitations) will be assessed by change from baseline in KCCQ-23 CSS and the effect on exercise capacity by change from baseline in peak oxygen consumption (pVO2). The 2 primary endpoints were selected to assess the symptoms and functional limitation reported most frequently as troublesome by participants with nHCM: exertional dyspnea, fatigue, and limited exercise capacity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Diagnosis of HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines: unexplained left-ventricular hypertrophy with non-dilated ventricular chambers in the absence of other cardiac or systemic disease which can produce the required magnitude of hypertrophy of a maximal LV wall thickness greater than or equal to 15 mm.
- •Peak LVOT pressure gradient < 30 mm Hg at rest and < 50 mm Hg with provocation.
- •New York Heart Association (NYHA) Class II or III.
- •KCCQ-23 CSS Score less than or equal to 80 at screening.
- •LVEF greater than or equal to 60%.
- •CPET: Documented oxygen saturation at rest > 90% at screening.
- •NT-proBNP greater than or equal to 200 pg/mL or BNP greater than or equal to 70 pg/mL.
- •Evidence of myocardial damage or Evidence of LV diastolic dysfunction.
排除标准
- •Known infiltrative or storage disorder causing cardiac hypertrophy that mimics nHCM.
- •History of unexplained syncope within 6 months prior to screening.
- •History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to screening.
- •Paroxysmal or persistent (non-permanent) AF detected at the time of screening.
- •ICD placement or pulse generator change within 2 months prior to screening or planned new ICD placement during the study.
- •Acute heart failure from 4 weeks prior to screening up to randomization.
- •Coronary artery disease requiring intervention.
- •Heart transplant recipient or listed for heart transplant.
- •Currently implanted LV assist device.
- •Clinically significant pulmonary disease associated with exertional dyspnea.
- •Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening.
- •Clinically documented LV aneurysm greater than or equal to 2 cm.
结局指标
主要结局
1) To assess the efficacy of a 48-week course of
时间窗: 1) Change from baseline in KCCQ-23 CSS at Week 4 | 2) Change from baseline in pVO2 at Week 48
capacity
时间窗: 1) Change from baseline in KCCQ-23 CSS at Week 4 | 2) Change from baseline in pVO2 at Week 48
mavacamten compared to placebo on patient reported health status
时间窗: 1) Change from baseline in KCCQ-23 CSS at Week 4 | 2) Change from baseline in pVO2 at Week 48
2) To assess the efficacy of a 48-week course of
时间窗: 1) Change from baseline in KCCQ-23 CSS at Week 4 | 2) Change from baseline in pVO2 at Week 48
mavacamten compared to placebo on exercise
时间窗: 1) Change from baseline in KCCQ-23 CSS at Week 4 | 2) Change from baseline in pVO2 at Week 48
次要结局
- Evaluate the effects of mavacamten on NYHA(classification)
- Evaluate the effects of mavacamten on(ventilatory efficiency as measured by the)
- Evaluate the effects of mavacamten on cardiac(biomarkers of myocardial injury)
- Evaluate the effects of mavacamten on composite of cardiovascular event(Time to first MACE-plus events defined as any CV death, non-fatal myocardial infarction, non-fatal stroke,)
- Evaluate the effects of mavacamten on patient reported shortness of breath(Change from baseline in HCMSQ SoB domain to Week 48)