Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Safety and Efficacy Study of CDR132L on Reverse Cardiac Remodeling in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Left atrial maximum volume
研究概览
简要总结
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study including approximately 130 randomized HF patients with heart failure with mildly reduced or preserved ejection fraction (LVEF ≥45%), to assess efficacy and safety of CDR132L on reverse remodeling. In this study, patients with HFpEF (EF ≥50%) or HFmrEF (LVEF 45-49%) will be included.
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)
盲法说明
IMP to be masked after preparation by unblinded staff.
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Provision of signed informed consent prior to any study-specific procedures.
- •Male or female of non-childbearing potential patients age ≥40 and <85 years.
- •Documented diagnosis of symptomatic heart failure (NYHA class II-IV) at enrollment, and a medical history of typical symptoms/signs of heart failure ≥6 weeks before enrollment with at least intermittent need for diuretic treatment.
- •Ejection fraction ≥45% (determined by echocardiography at site laboratory)
- •Increased intraventricular wall thickness (≥11 mm for female and ≥12 mm for male patients by echocardiography at site laboratory)
- •NT-proBNP > 300 pg/ml (sinus rhythm); >900 pg/ml (atrial fibrillation at time of screening/inclusion or documented with the last 6 months)
- •BMI between 22 kg/m² and 45 kg/m².
排除标准
- •Hemoglobin A1C (A1C) ≥10.5%
- •eGFR <35 mL/min/1.73m²
- •Systolic blood pressure (BP) <90 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
- •Systolic BP≥180 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
- •Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement.
- •Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
研究组 & 干预措施
CDR132L 4.52 mg
Six times CDR132L 4.52 mg/kg body weight intravenous in single dose.
干预措施: CDR132L (Drug)
Placebo
Six times Placebo intravenous in single dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Left atrial maximum volume
时间窗: 6 months
Left atrial maximum volume (measured by cardiac magnetic resonance imaging in end systole(indexed to the height in meters raised to the power of 2))
Total cardiac extracellular volume
时间窗: 6 months
Total cardiac extracellular volume (mL) measured by cardiac magnetic resonance imaging
Left atrial strain
时间窗: 6 months
Left atrial strain measured by cardiac magnetic resonance imaging
Concentration of N-terminal pro B-type natriuretic peptide
时间窗: 6 months
Concentration measured as biomarker from blood samples.
Maximum left ventricular wall thickness
时间窗: 6 months
Maximum left ventricular wall thickness measured by cardiac magnetic resonance imaging
Age-adjusted e' velocity
时间窗: 6 months
Age-adjusted e' velocity measured by doppler echocardiography. With e´velocity being the maximal velocity of mitral annular motion (E-wave).
Concentration of high-sensitivity cardiac troponin T
时间窗: 6 months
Concentration measured as biomarker from blood samples.
Left ventricular mass
时间窗: 6 months
Left ventricular mass measured by cardiac magnetic resonance imaging (indexed to the height in meters raised to the power of 2)
Global longitudinal strain
时间窗: 6 months
Global longitudinal strain measured by echocardiography
E/e'
时间窗: 6 months
E/e' measured by doppler echocardiography to evaluate the LV filling pressure.
次要结局
未报告次要终点