NCT06299826已完成2 期
A Phase IIb Two-Cohort, Randomised, Placebo-controlled, Double-blind, Multi-centre, Dose-ranging Study of AZD5462 in Stable Patients With Chronic Heart Failure
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 375
- 试验地点
- 58
- 主要终点
- Cohort A and B: Change from Baseline in Echocardiography Parameters
研究概览
简要总结
The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF).
详细描述
This is a Phase IIb randomized, double-blind, placebo-controlled, multi-center, dose-ranging study to evaluate the efficacy, safety, and pharmacokinetic (PK) of AZD5462 on top of standard of care in 2 cohorts of participants with HF: Cohort A, and Cohort B.
The study will include 3 periods and approximately 12 study visits:
- Screening period of up to 4 weeks (at least 1 study visit)
- Treatment period of 24 weeks (8 study visits)
- Follow-up period of 4 weeks (3 study visits)
Eligible participants in each cohort will be randomized equally 1:1:1:1 to receive a once daily dose (OD) of 3 dose levels (low, medium, or high) oral dose of AZD5462 tablets or placebo.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a pre-existing diagnosis of HF NYHA FC II to IV.
- •Participants must be on stable HF standard of care medication for at least 4 weeks prior to consent and during the Screening period.
- •Minimum body mass index (BMI) of 18 kilograms per meter square (kg/m^2) at Screening.
- •For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential.
- •All male participants should refrain from fathering a child or donating sperm until 3 months after the final study Follow-up Visit. Non-sterilised male participants should avoid fathering a child either by true abstinence or use of a condom for all sexual intercourse with a female partner of childbearing potential from the first dose until 3 months after the final Follow-up Visit.
排除标准
- •Historical or current evidence of a clinically significant disease or disorder including, but not limited to:
- •Myocardial infarction, stroke, transient ischaemic attack, coronary artery bypass grafting, or percutaneous coronary intervention within 12 weeks prior to consent or transcatheter structural heart interventions or cardiac valve surgery within 6 months prior to consent.
- •Sarcoidosis, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic (obstructive) cardiomyopathy.
- •History of untreated clinically significant valve disease or a Screening confirmation of severe aortic stenosis, severe mitral stenosis, moderate or severe aortic insufficiency or severe mitral insufficiency.
- •Amyloidosis, Fabry disease, or haemochromatosis.
- •Pericardial disease (i.e., visually significant white pericardium on echocardiogram).
- •Known coagulation disorders.
- •Current diagnosis of active hepatitis.
- •Severe pulmonary disease that is not expected to improve over time, as assessed by the investigator.
- •Decompensated HF or any cardiopulmonary hospitalisation, except planned hospitalisation without worsening of cardiac or pulmonary functions, within 4 weeks prior to consent or during the Screening period.
- •History of active malignancy within 2 years, except for fully excised or treated basal cell carcinoma, or ≤ 2 squamous cell carcinomas of the skin and participants who are under investigation for breast or cervical cancer, including participants with a pap smear of grade ≥
- •History of hypersensitivity to AZD5462 or any component of AZD5462 drug product.
- •Known history of drug or alcohol abuse within 24 months of Screening.
- •Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication.
- •Cardiac ventricular arrhythmia that requires treatment.
- •History of or anticipated heart transplant.
- •Current or planned cardiac resynchronization therapy/bi-ventricular pacemaker or mechanical assist device implantation.
- •Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter etc).
- •Positive hepatitis C antibody, or hepatitis B virus surface antigen at Screening. Participants with positive hepatitis B virus core antibody can be included in the study as long as hepatitis B virus surface antigen is negative, and there are no other signs of an active hepatitis B.
- •Known to have historically tested positive for Human Immunodeficiency Virus.
研究组 & 干预措施
Cohort A & B: Placebo
Experimental
Participants will receive matching placebo OD tablets for 24 weeks.
干预措施: Placebo (Drug)
Cohort A & B: AZD5462 low dose
Experimental
Participants will receive low dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462 (Drug)
Cohort A & B: AZD5462 high dose
Experimental
Participants will receive high dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462 (Drug)
Cohort A & B: AZD5462 medium dose
Experimental
Participants will receive medium dose of AZD5462 as OD tablets for 24 weeks.
干预措施: AZD5462 (Drug)
结局指标
主要结局
Cohort A and B: Change from Baseline in Echocardiography Parameters
时间窗: From Baseline to Week 25
To evaluate the effect of AZD5462 after treatment in participants with HF.
次要结局
- Cohort A and B: Change from Baseline in Echocardiography Parameters(From Baseline to Week 13 and Week 25)
- Cohorts A and B: Change from Baseline in Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS)(From Baseline to Weeks 3, 5, 13, and 25)
- Cohorts A and B: Change from Baseline in New York Heart Association Functional Class (NYHA FC)(Baseline and Week 25)
- Cohorts A and B: Change from Baseline in cardiac biomarkers(From Baseline to Weeks 5, 13, and 25)
- Cohorts A and B : Plasma Concentration of AZD5462(Day 15 (Week 3), Day 29 (Week 5) and 85 (Week 13))
- Cohorts A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Baseline to Week 29 (Day 197))
研究者
研究点 (58)
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