A Phase 2b/3, Randomized, Double-Blinded, Placebo Controlled Study ChecKing the Efficacy and Safety of ATAciguat to Slow the Progression of VaLvular DYsfunction in Participants With Moderate Calcific Aortic Valve STenosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,276
- 试验地点
- 106
- 主要终点
- (Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24
研究概览
简要总结
The purpose of this study is to evaluate if ataciguat slows the progression of moderate calcific aortic valve stenosis in adults.
详细描述
This study will be conducted in two parts: Part A and Part B. The purpose of Part A is to investigate whether ataciguat slows the progression of aortic valve calcium (AVC) deposition in adults with moderate calcific aortic valve stenosis (CAVS). The safety, tolerability, and pharmacokinetics of ataciguat will also be evaluated. Approximately 132 participants will be enrolled in Part A. Enrollment in Part B will begin once enrollment in Part A is complete. The purpose of Part B is to investigate whether ataciguat slows the rate of aortic valve area (AVA) loss and to evaluate the effect of ataciguat on peak oxygen consumption (VO2) in participants with moderate CAVS. The safety and tolerability of ataciguat will also be evaluated. Approximately 1144 participants will be enrolled in Part B.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female at least 50 years of age
- •Has moderate CAVS as defined by:
- •An AVA of ≥1.0 cm2 to ≤1.50 cm2
- •An AVC score between >300 to 1200 Agatston units (AU) for women and between >300 to 2000 AU for men
- •Has a left ventricular ejection fraction (EF) of ≥45% at the time of Screening as determined by the echocardiography Imaging Core Laboratory
- •For participants in CPET sub-study in Part A and all participants in Part B: If on beta blockade, the dose must be stable for at least 90 days prior to the Screening Visit with no anticipated changes during the study
排除标准
- •For participants in the CPET sub-study in Part A and all participants in Part B: Has any medical or physical condition that, in the Investigator's opinion, could lead to an inability to complete Protocol-required CPET procedures (eg, pulmonary disease, joint, leg, hip, back conditions that limit physical activity, or other absolute contraindications for CPET)
- •Anticipated or planned prior aortic valve replacement, repair, surgery, or intervention in the next 6 months
- •Has moderate, moderate-to-severe, or severe (Grade 2 or higher) mitral stenosis, mitral regurgitation, and/or aortic regurgitation
- •Has suspected or known congenital aortic valve disease including bicuspid aortic valve
- •New York Heart Association (NYHA) Class IV heart failure symptoms and/or requires continuous inotropes
- •Has history of hypertrophic, genetic/familial cardiomyopathy or cardiomyopathy related to amyloid or sarcoid
- •Has untreated obstructive coronary artery disease or anticipating coronary stenting surgery
- •Abnormal electrocardiogram (ECG) results or long-standing persistent or permanent atrial fibrillation
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Ataciguat
干预措施: Ataciguat (Drug)
结局指标
主要结局
(Part A) Change in Aortic Valve Calcium (AVC) score as assessed by non-contrast CT from baseline to Week 24
时间窗: Week 24
(Part B Dual-Primary) Percent change in Aortic Valve Area (AVA) as measured by echocardiogram from baseline to Week 48
时间窗: Week 48
(Part B Dual-Primary) Change in peak VO2 by CPET from baseline to Week 48
时间窗: Week 48
次要结局
- (Part A) Correlation in the change in AVC as assessed by non-contrast CT and change in VO2 at Week 48(Week 48)
- (Part A) Change in VO2 from baseline to Week 48(Week 48)
- Change in left ventricular diastolic function as assessed by E/e' from baseline to Week 48(Week 48)
- (Part A) Change in Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) from baseline to Week 48(Week 48)
- (Part B) Time to decision to proceed with TAVR/SAVR or all-cause death(Week 158)
- (Part B) Percentage of participants with progression to AVA <1.0cm2 at Week 48(Week 48)
- (Part A) Correlation in the change in AVC as assessed by non-contract CT and change in VO2 as assessed be remote cardiac monitoring devices at Week 48(Week 48)
- (Part A) Change in VO2 as assessed by remote cardiac monitoring devices from baseline to Week 48(Week 48)
- (Part A) Change in Left Ventricular Mass Index (LVMI) from baseline to Week 48(Week 48)
- (Part B) Change in AVC score as assessed by non-contrast CT from baseline to Week 48(Week 48)