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 (POWER-HF)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 281
- 试验地点
- 52
- 主要终点
- Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o LVEF as assessed by two-dimensional echocardiography (2D-echo) o Left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo o Left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo
研究概览
简要总结
• To evaluate the efficacy of JTT-861 administered for 12 weeks in subjects with heart failure with reduced ejection fraction (HFrEF) • To evaluate the safety and tolerability of JTT-861 administered for 12 weeks in subjects with HFrEF • To evaluate the pharmacokinetics (PK) of JTT-861 administered for 12 weeks in subjects with HFrEF
研究设计
- 分配方式
- Randomized
- 主要目的
- Double-blind Treatment Period
- 盲法
- Double (Investigator, Subject)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female, age 30-85 years (inclusive), at the Screening Visit;
- •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; Note: In the context of paced rhythm, the underlying cardiac rhythm should be considered when selecting the NT-pro-BNP cutoff level.
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 worsening 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.
结局指标
主要结局
Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o LVEF as assessed by two-dimensional echocardiography (2D-echo) o Left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo o Left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo
Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o LVEF as assessed by two-dimensional echocardiography (2D-echo) o Left ventricular end-systolic volume (LVESV) index as assessed by 2D-echo o Left ventricular end-diastolic volume (LVEDV) index as assessed by 2D-echo
Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o Left atrial volume (LAV) as assessed by 2D-echo o NT-pro-BNP o Kansas City Cardiomyopathy Questionnaire (KCCQ) scores
Efficacy Parameters • Change from baseline to end of treatment (EOT) in: o Left atrial volume (LAV) as assessed by 2D-echo o NT-pro-BNP o Kansas City Cardiomyopathy Questionnaire (KCCQ) scores
Pharmacokinetic (PK) Parameters • JTT-861 trough plasma concentrations at Weeks 4, 8 and 12 • JTT-861 plasma concentrations (post-dose) at Weeks 2, 4 and 8
Pharmacokinetic (PK) Parameters • JTT-861 trough plasma concentrations at Weeks 4, 8 and 12 • JTT-861 plasma concentrations (post-dose) at Weeks 2, 4 and 8
Safety Parameters • Number of subjects with adverse events (AEs), change from baseline in safety laboratory, vital signs and 12-lead electrocardiogram (ECG) parameters.
Safety Parameters • Number of subjects with adverse events (AEs), change from baseline in safety laboratory, vital signs and 12-lead electrocardiogram (ECG) parameters.
次要结局
- Exploratory Efficacy Parameters • Change from baseline to EOT in: o eGFR o Cystatin C o Urine albumin-to-creatinine ratio (ACR) o Hemoglobin A1c (HbA1c) and plasma glucose
- Exploratory Efficacy Parameters • Change from baseline to EOT in: o Tricuspid annular plane systolic excursion (TAPSE) as assessed by 2D-echo o Fractional area change (FAC) as assessed by 2D-echo o Right ventricular (RV) longitudinal strain as assessed by 2D-echo o Tricuspid regurgitation peak gradient (TRPG) as assessed by 2D-echo
- Exploratory Pharmacodynamic (PD) Parameters • Change from baseline to EOT in branched-chain amino acids (BCAAs: isoleucine, leucine and valine) and alanine plasma concentrations
研究者
Osamu Yamada
Scientific
Akros Pharma Inc.