A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of CRD-4730 in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 525
- 试验地点
- 2
- 主要终点
- Change from Baseline in Composite Z-Score at 24 weeks
研究概览
简要总结
CRD-4730 is a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. The CALIBRATE-HF trial is a Phase 2, global, multi-center, randomized, double-blind, parallel-group, placebo-controlled trial. The trial will evaluate the efficacy, safety, and tolerability of CRD-4730 in addition to guideline directed medical therapy in participants with heart failure with reduced ejection fraction (HFrEF). Participants will be randomized to 1 of 4 study groups and receive investigational study drug or placebo twice daily (BID) for 24 weeks of treatment.
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
- •Adult male or female patient ≥ 18 years of age and ≤ 85 years of age at the time of screening.
- •Has a medical history supporting a diagnosis of clinical chronic heart failure (HF) syndrome with a duration of at least 8 weeks prior to the time of screening and current NYHA functional class II to III (based on investigator's assessment).
- •Has left ventricular ejection fraction ≤ 40% by a centrally read transthoracic echocardiogram performed during screening.
- •Has NT-proBNP level ≥ 600 pg/mL (70.8 pmol/L) at the time of screening. Patients in atrial fibrillation or flutter at the time of screening are required to have an NT-proBNP level of ≥ 900 pg/mL (106.4 pmol/L).
- •Is receiving optimized and stable guideline directed HF therapy (per applicable regional or national guidelines).
排除标准
- •Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 4 weeks of the time of screening or during the Screening Period.
- •Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration.
- •Has acute coronary syndrome, unstable angina, persistent angina at rest, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, cardiac valve repair (surgical or nonsurgical) or surgical replacement, or carotid angioplasty within 8 weeks prior to screening or during the Screening Period.
- •Has clinical suspicion of infiltrative cardiomyopathy (eg, amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Study Arm 3: CRD-4730 Dose C tablet
Participants will receive Dose C of CRD-4730 administered orally twice daily for 24 weeks
干预措施: CRD-4730 (Drug)
Study Arm 1: CRD-4730 Dose A tablet
Participants will receive Dose A of CRD-4730 administered orally twice daily for 24 weeks
干预措施: CRD-4730 (Drug)
Study Arm 4: Matched Placebo tablet
Participants will receive placebo administered orally twice daily for 24 weeks
干预措施: Placebo (Drug)
Study Arm 2: CRD-4730 Dose B tablet
Participants will receive Dose B of CRD-4730 administered orally twice daily for 24 weeks
干预措施: CRD-4730 (Drug)
结局指标
主要结局
Change from Baseline in Composite Z-Score at 24 weeks
时间窗: Baseline and Week 24
Composite Z-score calculated as the average of Z-scores for the change from baseline at 24 weeks for the following 6 endpoints: NT-proBNP (log-transformed), Left ventricular end-diastolic volume index (LVEDVI), Left ventricular end-systolic volume index (LVESVI), E/e' ratio, Global longitudinal strain (GLS), Left atrial volume index (LAVI). A z-score for each component endpoint is a standardized measure with a common scale with a mean of 0 and a standard deviation of 1. Composite z-score integrates the component z-scores to assess a participant's overall response. Lower composite z-scores indicate more favorable changes from baseline, whereas higher composite z-scores indicate less favorable changes from baseline.
次要结局
- NT-proBNP biomarker(Baseline, Week 12, and Week 24)
- Left ventricular end-diastolic volume(Baseline, Week 12, and Week 24)
- Left ventricular end-diastolic volume index(Baseline, Week 12, and Week 24)
- Left ventricular end-systolic volume(Baseline, Week 12, and Week 24)
- Left ventricular end-systolic volume index(Baseline, Week 12, and Week 24)
- Early diastolic mitral inflow velocity (E)/early diastolic mitral annular velocity (e') ratio(Baseline, Week 12, and Week 24)
- Global longitudinal strain(Baseline, Week 12, and Week 24)
- Left atrial volume index(Baseline, Week 12, and Week 24)
- Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary score(Baseline, Week 12 and Week 24)
- Kansas City Cardiomyopathy Questionnaire (KCCQ) Total summary score(Baseline, Week 12, and Week 24)
- Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary score(Baseline, Week 12, and Week 24)