A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2
- Conditions
- Pulmonary Hypertension (World Health Organization Group 2)Heart Failure
- Interventions
- Drug: Placebo
- Registration Number
- NCT05737940
- Lead Sponsor
- AstraZeneca
- Brief Summary
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
- Detailed Description
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.
The expected total duration of the study is 32 to 37 weeks, depending on the length of the Screening Period.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 260
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD3427 Dose A AZD3427 The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155. AZD3427 Dose B AZD3427 The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155. Placebo Placebo The participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155. AZD3427 Dose C AZD3427 The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155.
- Primary Outcome Measures
Name Time Method Change from baseline in Pulmonary Vascular Resistance (PVR) 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.
- Secondary Outcome Measures
Name Time Method Change from baseline in Mean pulmonary arterial pressure (mPAP) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on mPAP parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in Pulmonary artery wedge pressure (PAWP) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on PAWP parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in cardiac output Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on cardiac output parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in Stroke Volume (SV) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on SV parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in Ejection fraction (EF) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on EF parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in left ventricular global longitudinal strain (LVGLS) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on LVGLS parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in pulmonary arterial systolic pressure (PASP) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in right ventricle/left ventricle (RV/LV) ratio Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on RV/LV parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in right ventricular outflow tract acceleration time (RVOT AT) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on RVOT AT parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in Tricuspid regurgitation velocity (TRV) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on TRV parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in TAPSE/PASP [Tricuspid annular plane systolic excursion/ Pulmonary arterial systolic pressure] Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on TAPSE/PASP parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in systemic vascular resistance Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on systemic vascular resistance parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in 6-minute walking distance (6MWD) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on function and symptoms using 6MWD parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ TSS) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on function and symptoms using KCCQ TSS parameter after 24 weeks of treatment in participants with HF and PH Group 2. The score ranges from 0 to 100, where a higher score represents a better patient outcome.
Change from baseline in New York Heart Association Functional Class (NYHA FC) Baseline to Week 25 To evaluate the effect of AZD3427 compared with placebo on function and symptoms using NYHA FC parameter after 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in serum creatinine Baseline to Week 13 and Week 25 To evaluate the effect of AZD3427 compared with placebo using serum creatinine parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) Baseline to Week 13 and Week 25 To evaluate the effect of AZD3427 compared with placebo using NT-proBNP parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in cystatin C Baseline to Week 13 and Week 25 To evaluate the effect of AZD3427 compared with placebo using cystatin C parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.
Change from baseline in eGFR (estimated glomerular filtration rate) Baseline to Week 13 and Week 25 To evaluate the effect of AZD3427 compared with placebo using eGFR parameter after 12 and 24 weeks of treatment in participants with HF and PH Group 2.
Pharmacokinetics (AZD3427 serum exposure) On Day 15, Day 29, Day 85, Day 127, Day 169, and Day 211 Serum concentration of AZD3427 summarised by timepoints and dose level.
Number of participants with presence of Anti-drug antibodies (ADAs) On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211 To evaluate the immunogenicity of AZD3427 using ADA parameter.
Evaluation of positive ADA titer On Day 1, Day 15, Day 29, Day 85, Day 169, and Day 211 To evaluate the immunogenicity of AZD3427 as measured by ADAs.
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom