A Phase IIb Randomised, Double-blind, Placebo-controlled, Multi-centre, Dose-ranging Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Due to Left Heart Disease (WHO Group 2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Change from baseline in Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
This study is intended to assess the ability of AZD3427 to reduce pulmonary vascular resistance (PVR) after 24 weeks of treatment in participants with heart failure (HF) and pulmonary hypertension (PH) Group 2
详细描述
This study is a randomized, placebo-controlled, multi-centre, dose-ranging study of AZD3427 in participants with heart failure and pulmonary hypertension due to left heart disease (World Health Organisation [WHO] Group 2).
Approximately 220 participants will be randomised to 4 treatment groups (in a 1:1:1:1 ratio) to receive a subcutaneous (SC) injection of AZD3427 or placebo every 2 weeks for 24 weeks.
This study will evaluate 3 dose levels of AZD3427: Dose A, Dose B, and Dose C. Dose modification is not applicable for this study.
The study will be conducted in approximately 60 study centres across an estimated 15 countries.
The study will include approximately 16 study visits: 2 visits during the Screening Period,13 visits during the Treatment Period, and one visit during the Follow-up Period.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
AZD3427 Dose A
The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155.
干预措施: AZD3427 (Drug)
AZD3427 Dose B
The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155.
干预措施: AZD3427 (Drug)
AZD3427 Dose C
The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155.
干预措施: AZD3427 (Drug)
Placebo
The participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in Pulmonary Vascular Resistance (PVR)
时间窗: Baseline to Week 25
To evaluate the effect of AZD3427 on PVR parameter compared with placebo as measured by right heart catheterization (RHC) after 24 weeks of treatment in participants with HF and PH Group 2.
次要结局
- Change from baseline in Mean pulmonary arterial pressure (mPAP)(Baseline to Week 25)
- Change from baseline in Pulmonary artery wedge pressure (PAWP)(Baseline to Week 25)
- Change from baseline in cardiac output(Baseline to Week 25)
- Change from baseline in Stroke Volume (SV)(Baseline to Week 25)
- Change from baseline in Ejection fraction (EF)(Baseline to Week 25)
- Change from baseline in left ventricular global longitudinal strain (LVGLS)(Baseline to Week 25)
- Change from baseline in pulmonary arterial systolic pressure (PASP)(Baseline to Week 25)
- Change from baseline in right ventricle/left ventricle (RV/LV) ratio(Baseline to Week 25)
- Change from baseline in right ventricular outflow tract acceleration time (RVOT AT)(Baseline to Week 25)
- Change from baseline in Tricuspid regurgitation velocity (TRV)(Baseline to Week 25)
- Change from baseline in TAPSE/PASP [Tricuspid annular plane systolic excursion/ Pulmonary arterial systolic pressure](Baseline to Week 25)
- Change from baseline in systemic vascular resistance(Baseline to Week 25)
- Change from baseline in 6-minute walking distance (6MWD)(Baseline to Week 25)
- Change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ TSS)(Baseline to Week 25)
- Change from baseline in New York Heart Association Functional Class (NYHA FC)(Baseline to Week 25)
- Change from baseline in serum creatinine(Baseline to Week 13 and Week 25)
- Change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)(Baseline to Week 13 and Week 25)
- Change from baseline in cystatin C(Baseline to Week 13 and Week 25)
- Change from baseline in eGFR (estimated glomerular filtration rate)(Baseline to Week 13 and Week 25)
- Pharmacokinetics (AZD3427 serum exposure)(On Day 15, Day 29, Day 85, Day 127, Day 169, and Day 211)
- Number of participants with presence of Anti-drug antibodies (ADAs)(On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211)
- Evaluation of positive ADA titer(On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211)