Study to Evaluate the Effects of AZD3427 in Patients With Heart Failure

NCT04890548 | Withdrawn Phase 1

• 1 other identifier: D8330C00002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Heart Failure

Keywords

Heart Failure with Preserved Ejection Fraction; Heart Failure with Reduced Ejection Fraction; Forearm blood flow

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1

Secondary Outcomes (3)

• Number of patients with anti-drug antibody (ADAs) in serum samples at baseline and at Day 8, Day 29, and Day 50

  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

  Day 1

• Change from baseline in forearm blood flow ratio between arms (infused arm:non-infused arm) after each AZD3427 IA infusion

  Day 1

Other Outcomes (1)

• Number of patients with adverse events

  From Screening (Day -42 to Day -1) until the Follow-up visit (Day 1, Day 2, Day 8, Day 29, and Day 50)

Study Arms (1)

Patients with HFpEF or HFrEF

EXPERIMENTAL

Patients will be enrolled in 2 cohorts in parallel: 1 cohort of patients with HFpEF and 1 cohort of patients with HFrEF. Patients will receive a sequence of 5 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.

Drug: AZD3427

Interventions

AZD3427 DRUG

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.

Patients with HFpEF or HFrEF

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be 18 to 75 years of age.
• Patient with known clinical diagnosis of Stage C heart failure New York Heart Association (NYHA) Class I-III and on stable medical therapy for at least 12 weeks prior to screening with no significant dose change or new medications added during that period. Specifically:
• Patients with a diagnosis of HFrEF, defined as ejection fraction ≤ 40%. OR
• Patients with a diagnosis of HFpEF, defined as ejection fraction ≥ 50%.
• Patients with suitable veins and arteries for cannulation or repeated puncture.
• Patients who are able to lie flat for the duration of IA infusions and related procedures during Visit 2 (approximately 3 hours).
• Body weight of at least 60 kg and body mass index within the range of 18 to 40 kg/m\^2.
• Male and/or female of nonchildbearing potential.
• Capable of giving signed informed consent.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• Clinically significant valvular heart disease as judged by the investigator.
• Congenital heart disease (patients with Patent Foramen Ovale may be included in the study).
• Clinical diagnosis of heart failure NYHA Class IV.
• Occurrence in the last 3 months of any of the following:
• Acute coronary syndrome: myocardial infarction or unstable angina.
• Percutaneous coronary intervention.
• Cerebrovascular accident or transient ischaemic attack.
• Heart failure hospitalisation.
• History of prior dissections.
• History or suspicion of cardiac amyloidosis.
• Patients with conditions where vasodilator therapy may be contraindicated.
• History of cancer in the last 5 years, except for non-melanoma skin cancer.
• Any clinically important abnormalities in clinical chemistry, haematology or urinalysis.
• Any positive result at Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 18, 2021
• Study Start: November 23, 2021
• Primary Completion: August 2, 2022
• Study Completion: August 2, 2022
• Last Updated: December 17, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure