A Phase 3, Multi-center, Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 175
- 试验地点
- 105
- 主要终点
- Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who meet all the following criteria at screening may be included in the trial:
- •Males and females between 18 to 85 years of age, inclusive, at screening
- •Body mass index < 35 kg/m2
- •Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -
- •Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and
- •Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory:
- •≥ 15 mm in one or more myocardial segments OR
- •≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM
- •New York Heart Association (NYHA) class II or III
- •Has a Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) score of ≤ 90 at screening
- •Has a screening echocardiogram with the following determined by the echocardiography core laboratory:
- •Resting left ventricular outflow tract gradient (LVOT-G) > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
- •LVEF ≥ 60%
- •Hemoglobin ≥ 10g/dL
- •Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) < 100% predicted on the screening cardiopulmonary exercise testing (CPET) per the core laboratory
- •Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks
排除标准
- •Any of the following criteria will exclude potential participants from the trial:
- •Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
- •History of intolerance or medical contraindication to beta blocker therapy
- •Resting Systolic Blood Pressure (SBP) of > 160 mmHg
- •Resting heart rate of > 100 bpm
- •Significant valvular heart disease
- •Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
- •Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)
- •Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
- •History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any time during their clinical course
- •Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
- •Documented room air oxygen saturation reading < 90% at screening
- •Planned septal reduction treatment that cannot be deferred during the trial period
- •History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
- •History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.
- •Current or recent (< 4 weeks) therapy with disopyramide
- •History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
- •Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten
研究组 & 干预措施
Aficamten up to 20 mg plus placebo for metoprolol
Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.
干预措施: Placebo to match metoprolol succinate (Drug)
Aficamten up to 20 mg plus placebo for metoprolol
Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.
干预措施: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg) (Drug)
Metoprolol succinate up to 200 mg plus placebo for aficamten
Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.
干预措施: Placebo to match aficamten (Drug)
Metoprolol succinate up to 200 mg plus placebo for aficamten
Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.
干预措施: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg) (Drug)
结局指标
主要结局
Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
时间窗: Baseline to Week 24
Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM
次要结局
- Change in left ventricular mass index (LVMI)(Baseline to Week 24)
- Change in left atrial volume index (LAVI)(Baseline to Week 24)
- Change from baseline values in NT-proBNP(Baseline to Week 24)
- Change in post-Valsalva LVOT-G(Baseline to Week 24)
- Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)(Baseline to Week 24)
- Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class(Baseline to Week 24)