A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety and Tolerability of JTT-861 Administered for 12 Weeks in Subjects With Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 314
- 试验地点
- 114
- 主要终点
- Post-dose plasma concentrations of JTT-861
研究概览
简要总结
This study will evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-861 administered once daily for 12 weeks in subjects with heart failure with reduced ejection fraction (HFrEF) who are on a stable, guideline-directed medical therapy for heart failure.
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
- 30 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a clinical diagnosis of symptomatic heart failure (HF) ≥90 days prior to the Screening Visit;
- •Is in New York Heart Association (NYHA) functional class II or III at the Screening Visit;
- •Is on stable, guideline-directed therapy for HF, consistent with American Heart Association (AHA), American College of Cardiology (ACC), Heart Failure Society of America (HFSA) or European Society of Cardiology (ESC) guidelines for ≥4 weeks prior to the Screening Visit (with at least half of maximal labeled dose of renin-angiotensin-aldosterone system (RAAS) inhibitors and β-blockers, if tolerated);
- •Has left ventricular ejection fraction (LVEF) ≤35% at the Screening Visit;
- •Has a serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) level ≥600 pg/mL (or ≥900 pg/mL if the subject has atrial fibrillation or atrial flutter) at the Screening Visit.
排除标准
- •Has a confirmed acute myocardial infarction (MI) (i.e., Type 1) or unstable angina within 90 days prior to the Screening Visit;
- •Has a history of coronary revascularization (percutaneous coronary intervention [PCI] and/or coronary artery bypass graft [CABG]) or other cardiovascular surgery within 90 days prior to the Screening Visit or planned cardiovascular surgery during the study through the Follow-up Visit);
- •Has started cardiac resynchronization therapy (CRT) within 90 days prior to the Screening Visit or has planned CRT during the study through the Follow-up Visit;
- •Has clinically significant congenital heart disease, active myocarditis or constrictive pericarditis;
- •Has current acute decompensated HF requiring additional treatment with diuretics, vasodilators and/or inotropic medications at the Screening Visit;
- •Has clinically significant chronic renal insufficiency (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation) at the Screening Visit.
研究组 & 干预措施
JTT-861 Dose 2
JTT-861 Capsules Dose 2 orally once daily for 12 weeks
干预措施: JTT-861 Capsules (Drug)
Placebo
Placebo Capsules orally once daily for 12 weeks
干预措施: Placebo Capsules (Drug)
JTT-861 Dose 1
JTT-861 Capsules Dose 1 orally once daily for 12 weeks
干预措施: JTT-861 Capsules (Drug)
结局指标
主要结局
Post-dose plasma concentrations of JTT-861
时间窗: Weeks 2, 4 and 8
Change from baseline to EOT in left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo
时间窗: 12 Weeks
Change from baseline to EOT in N-terminal pro b-type natriuretic peptide (NT-pro-BNP) values
时间窗: 12 Weeks
Change from baseline to end of treatment (EOT) in left ventricular ejection fraction (LVEF) as assessed by two-dimensional echocardiography (2D-echo)
时间窗: 12 Weeks
Change from baseline to EOT in left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo
时间窗: 12 Weeks
Change from baseline to EOT in left atrial volume (LAV) as assessed by 2D-echo
时间窗: 12 Weeks
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores from baseline
时间窗: 16 Weeks
General Scoring Guideline: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent
Number of subjects with treatment-emergent adverse events
时间窗: Up to 16 Weeks
Trough plasma concentrations of JTT-861
时间窗: Weeks 4, 8 and 12
次要结局
未报告次要终点