COR-1, an Anti-Beta1 Receptor Antibody Cyclopeptide in Heart Failure: a Phase II, Multicentre, Randomised, Double-Blind and Placebo-Controlled Study With Parallel Groups
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 主要终点
- Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6
研究概览
简要总结
The purpose of this study is to investigate the effect of COR-1 in combination with standard therapy in patients with heart failure. The safety and tolerability of COR-1 will also be assessed.
详细描述
In patients with dilated cardiomyopathy (heart is weakened and enlarged), the presence of anti-beta1-receptor autoantibodies has been shown to predict more depressed left ventricular function, increased prevalence of serious ventricular arrhythmias, sudden cardiac death, and cardiovascular mortality. In animal models, COR-1 cyclopeptide has been shown to bind to, and therefore decrease, the anti-beta1-receptor autoantibody titre. This study will investigate the safety and effectiveness of COR-1 treatment in patients with dilated cardiomyopathy. This study will be a randomized (the study treatment is assigned by chance), double-blind, (neither investigator nor patient knows the treatment that the volunteer receives), multicenter (study is conducted in more than one center) placebo-controlled (one of the treatments is inactive), parallel group study (patients in different treatment groups receive medication at the same time) in men and women who have heart failure due to dilated cardiomyopathy. Eligible patients should also have a left ventricular ejection fraction of less than or equal to 45% (measurement of the percentage of blood leaving the heart each time it contracts) and should be positive for anti-beta1-receptor autoantibodies. The study will consist of 3 phases: a screening phase, a double-blind treatment period, and a follow-up phase. Patients will be randomly assigned to 1 of 4 treatment groups: 20 mg COR-1, 80 mg COR-1, 160 mg COR-1, or placebo (inactive medication). Each patient will receive 1 intravenous dose (medication is injected into a vein) every 4 weeks for a total of 6 months. Patients will come to the study center each time they receive study medication and will remain at the center for 2 to 3 hours following the injection. Blood samples will be drawn at time points during the screening, treatment, and follow-up periods. Patients will return to the study center for follow-up visits at 3 months following completion of the 6-month treatment period. Patients will participate in the study for approximately 9 months. Patient safety will be monitored. The study drug (COR-1) is being investigated for the treatment of 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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed heart failure due to dilated cardiomyopathy with left ventricular ejection fraction < 45%
- •Presence of anti-beta1-receptor autoantibodies
- •New York Heart Association (NYHA) class II to III heart failure
- •Symptomatic heart failure for >1 year and < 8 years
- •Treatment with adequate doses of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, and optional aldosterone antagonists according to guidelines for at least six months (with the exception of lack of tolerability of any of these drugs) and at stable doses for 2 months prior to screening
排除标准
- •Ischemic heart disease characterized by >= 50% coronary artery stenosis and/or history of myocardial infarction
- •Third or higher degree valvular defect
- •Any disease requiring immunosuppressive drugs (except for <= 5 mg/day prednisone-equivalent dose) or any clinically relevant disorder of the immune system
- •History of severe allergies and increased risk for anaphylactic shock (e.g., bronchial asthma)
- •History of, or currently active illness, considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results
研究组 & 干预措施
20 mg COR-1
干预措施: COR-1 (Drug)
Placebo
干预措施: Standard therapy for heart failure (Drug)
Placebo
干预措施: 0.9 % sodium chloride (Drug)
20 mg COR-1
干预措施: Standard therapy for heart failure (Drug)
80 mg COR-1
干预措施: COR-1 (Drug)
80 mg COR-1
干预措施: Standard therapy for heart failure (Drug)
160 mg COR-1
干预措施: COR-1 (Drug)
160 mg COR-1
干预措施: Standard therapy for heart failure (Drug)
结局指标
主要结局
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6
时间窗: Baseline and Month 6
The LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). Ejection fraction percentages greater than (\>) 55% are considered normal. It was measured by biplane echocardiography (central assessment).
次要结局
- Change From Baseline in Local Left Ventricular Ejection Fraction (LVEF) at Month 9(Baseline and Month 9)
- Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-ProBNP) Level at Month 6(Baseline and Month 6)
- Change From Baseline in Central Transmitral Flow Velocity Time Integral (VTI) at Month 6(Baseline and Month 6)
- Change From Baseline in Central Tissue E-Wave Doppler Mitral Annular Velocity at Month 6(Baseline and Month 6)
- Change From Baseline in Distance Walked During Six-minute Walk Test at Month 6(Baseline and Month 6)
- Number of Participants With New York Heart Association (NYHA) Classification of Disease Progression(Baseline and Month 6)
- Change From Baseline in Minnesota Living With Heart Failure Questionnaire Score at Month 6(Baseline and Month 6)
- Change From Baseline in Holter Electrocardiography (ECG) Parameters (Heart Rate) at Month 6(Baseline and Month 6)
- Number of Participants With Holter Electrocardiography (ECG) Parameters(Baseline and Month 6)