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

Study identifier:D8330C00002

ClinicalTrials.gov identifier:NCT04890548

EudraCT identifier:N/A

CTIS identifier:N/A

Will Be Recruiting

Official Title

A Mechanistic Study to Evaluate the Vasodilatory Effects of AZD3427 in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF) and Patients with Heart Failure with Reduced Ejection Fraction (HFrEF)

Medical condition

heart failure

Phase

Phase 1

Healthy volunteers

Study drug

AZD3427

Sex

All

Estimated Enrollment

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 23 Nov 2021

Estimated Primary Completion Date: 02 Aug 2022

Estimated Study Completion Date: 02 Aug 2022

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2021 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

1. Patient must be 18 to 75 years of age.
2. 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:
(a) Patients with a diagnosis of HFrEF, defined as ejection fraction ≤ 40%.
OR
(b) Patients with a diagnosis of HFpEF, defined as ejection fraction ≥ 50%.
3. Patients with suitable veins and arteries for cannulation or repeated puncture.
4. Patients who are able to lie flat for the duration of IA infusions and related procedures during Visit 2 (approximately 3 hours).
5. Body weight of at least 60 kg and body mass index within the range of 18 to 40 kg/m^2.
6. Male and/or female of nonchildbearing potential.
7. Capable of giving signed informed consent.

Exclusion Criteria

1. 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.
2. Clinically significant valvular heart disease as judged by the investigator.
3. Congenital heart disease (patients with Patent Foramen Ovale may be included in the study).
4. Clinical diagnosis of heart failure NYHA Class IV.
5. Occurrence in the last 3 months of any of the following:
(a) Acute coronary syndrome: myocardial infarction or unstable angina.
(b) Percutaneous coronary intervention.
(c) Cerebrovascular accident or transient ischaemic attack.
(d) Heart failure hospitalisation.
6. History of prior dissections.
7. History or suspicion of cardiac amyloidosis.
8. Patients with conditions where vasodilator therapy may be contraindicated.
9. History of cancer in the last 5 years, except for non-melanoma skin cancer.
10. Any clinically important abnormalities in clinical chemistry, haematology or urinalysis.
11. Any positive result at Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
12. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator.
13. Abnormal vital signs, after at least 10-minute supine rest, defined as any of the following at Screening:
(a) Systolic blood pressure (BP) > 160 mmHg.
(b) Diastolic BP > 90 mmHg.
14. Any clinically important abnormalities in rhythm, conduction or morphology of the
resting 12-lead electrocardiogram as considered by the investigator.
(a) Prolonged QTcF > 450 ms.
(b) Family history of long QT syndrome.
(c) Second or third-degree AV block, or sinus node dysfunction with significant sinus
pause.
15. History of hypersensitivity to drugs with a similar chemical structure or class to AZD3427.
16. Participants who have previously received AZD3427.

No locations available

Arms	Assigned Interventions
Experimental: Patients with HFpEF or HFrEF 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 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.

Arms

Assigned Interventions

Experimental: Patients with HFpEF or HFrEF
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
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.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]