The primary purpose of this mechanistic study is to evaluate the vasodilatory effects of AZD3427 in adult patients with heart failure and will be performed at approximately 2 study sites in the United Kingdom.
The study will enroll patients in 2 cohorts in parallel: 1 cohort of patients with heart failure with preserved ejection fraction (HFpEF) and 1 cohort of patients with heart failure with reduced ejection fraction (HFrEF). Each cohort plans to enroll at least 7 evaluable patients. All patients will receive the same sequence of 5 intra-arterial (IA) infusions into the brachial artery, consisting of a baseline saline infusion of approximately 20 minutes, followed by 3 sequential infusions of AZD3427 at ascending doses of approximately 10 minutes (each) and a washout saline infusion of approximately 15 minutes. For each patient, the study will last at least 51 days and up to 99 days, including: * A screening period of 1 to 42 days (which will include baseline echocardiography) * A single-day treatment period during which patients will stay at study site until at least 4 hours after the end of infusions * A follow-up period of 49 to 56 days after the end of the last infusion including: A follow-up phone call on Day 2 (within 24 ± 6 hours post-infusion) A follow-up visit on Day 8 (+ 3 days) A follow-up visit on Day 29 (± 2 days) A follow-up visit on Day 50 (+ 7 days)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Patients will receive 5 IA infusions of AZD3427 into the brachial artery. The IA infusions of AZD3427 will be administered via a syringe pump, using a polypropylene syringe containing 0.9% (w/v) saline and delivered through an administration set comprising a syringe, extension tubing (PVC), and a 0.2- or 0.22-μm PVDF syringe filter.
Maximum change from baseline in absolute forearm blood flow in the infused arm during AZD3427 IA infusions
To determine whether AZD3427 produces a vasodilatory response in the forearm resistance vessels of HFpEF and HFrEF patients, as assessed by forearm blood flow parameters measured using venous occlusion plethysmography.
Time frame: Day 1
Number of patients with anti-drug antibody (ADAs) in serum samples at baseline and at Day 8, Day 29, and Day 50
To assess the immunogenicity of AZD3427.
Time frame: Day 1, Day 8, Day 29 and Day 50
Change from baseline in forearm blood flow ratio in the infused arm (AZD3427 infusion:baseline) after each AZD3427 IA infusion
To determine whether AZD3427 produces a vasodilatory response in the forearm resistance vessels of HFpEF and HFrEF patients, as assessed by forearm blood flow parameters measured using venous occlusion plethysmography.
Time frame: Day 1
Change from baseline in forearm blood flow ratio between arms (infused arm:non-infused arm) after each AZD3427 IA infusion
To determine whether AZD3427 produces a vasodilatory response in the forearm resistance vessels of HFpEF and HFrEF patients, as assessed by forearm blood flow parameters measured using venous occlusion plethysmography.
Time frame: Day 1
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