A Randomized, Double-blind, Placebo-controlled Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 21
- 主要终点
- Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multi-center study in the United States (U.S.) that will evaluate the effect of mavacamten treatment on reducing the number of septal reduction therapy (SRT) procedures performed in subjects with symptomatic obstructive hypertrophic cardiomyopathy (oHCM [also known as HOCM]) who are eligible for SRT based on ACCF/AHA 2011 and/or ESC 2014 guidelines.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years old at screening and body weight > 45 kg at screening
- •Diagnosed with oHCM consistent with current ACCF/AHA 2011 and meet their recommendations for invasive therapies
- •Referred or under active consideration within the past 12 months for SRT procedure and willing to have SRT procedure
- •Has documented left ventricular ejection fraction (LVEF) ≥ 60% at Screening
- •Has documented oxygen saturation at rest ≥ 90% at Screening
排除标准
- •Persistent or permanent atrial fibrillation and subject not on anticoagulation for ≥ 4 weeks prior to screening and/or not adequately rate controlled ≤ 6 months prior to screening
- •Previously treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA])
- •For individuals on beta blockers, calcium channel blockers, or disopyramide, any dose adjustment of these medications < 14 days prior to screening or an anticipated change in regimen during the first 16 weeks of the study
- •Any medical condition that precludes upright exercise stress testing
- •Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at screening
- •Prior treatment with cardiotoxic agents, such as doxorubicin or similar
- •Has a history or evidence of any other clinically significant disorder, condition, or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
研究组 & 干预措施
Drug: Mavacamten
Mavacamten Capsules
Other names:
MYK-461
干预措施: Mavacamten (Drug)
Drug: Placebo
Matching Placebo Capsules
干预措施: Placebo (Drug)
结局指标
主要结局
Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16
时间窗: Week 16
Participants who decided to proceed with SRT or were eligible for SRT at week 16. Participants with missing assessments were classified as meeting the primary endpoint (did not improve). SRT eligibility using the New York Heart Association Functional Class (NYHA) and left ventricular outflow tract (LVOT) assessments per the 2011 ACCF/AHA guideline clinical and hemodynamic criterion are below: * NYHA Class III or IV/ NYHA Class II with exertion-induced syncope/near syncope, AND * Dynamic LVOT gradient at rest or with provocation \>= 50 mmHg. NYHA Class II at week 16, the following rules will be applied: * NYHA Class II with history of exertional syncope/ syncope at baseline and at W16 is still NYHA Class II, they remain SRT eligible IF their maximal LVOT gradient is ≥ 50mmHg * NYHA Class III/IV at baseline and at W16 has improved to Class II, they are no longer SRT eligible UNLESS they have AE of exertional syncope or pre-syncope during the 16 weeks.
次要结局
- Number of Participants With at Least One Class Improvement From Baseline in New York Heart Association (NYHA) Class at Week 16(Baseline and week 16)
- Change From Baseline to Week 16 in Kansas City Cardiomyopathy Questionnaire 23-item Version, Clinical Summary Score (KCCQ-23, CSS)(Baseline and week 16)
- Change From Baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP)(Baseline and week 16)
- Change From Baseline to Week 16 in Post-Exercise Left Ventricular Outflow Tract (LVOT) Gradient(Baseline and week 16)
- Change From Baseline to Week 16 in Cardiac Troponin(Baseline and week 16)