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Heart FailurePhase 1NCT04890548

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

A Phase 1 study testing AZD3427 in people with Heart Failure, run by AstraZeneca.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Heart Failure
What is being tested?
AZD3427
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
23 Nov 2021to 2 Aug 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator.
  • Abnormal vital signs, after at least 10-minute supine rest, defined as any of the following at Screening:
  • Systolic blood pressure (BP) > 160 mmHg.
  • Diastolic BP > 90 mmHg.
  • Any clinically important abnormalities in rhythm, conduction or morphology of the resting 12-lead electrocardiogram as considered by the investigator.
  • Prolonged QTcF > 450 ms.
  • Family history of long QT syndrome.
  • Second or third-degree AV block, or sinus node dysfunction with significant sinus pause.
  • History of hypersensitivity to drugs with a similar chemical structure or class to AZD3427.
  • Participants who have previously received AZD3427.

About this study

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)

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.

Read the detailed description

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)

Conditions
Heart Failure
Being tested
AZD3427
Keywords
Heart Failure with Preserved Ejection Fraction, Heart Failure with Reduced Ejection Fraction, Forearm blood flow
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD3427Drug

    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.

Study groups in NCT04890548
Study groupRoleWhat they receive
Patients with HFpEF or HFrEFExperimentalPatients 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.
Receives: Drug: AZD3427

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 1

Secondary outcomes (3)

  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.

    Measured: Day 1, Day 8, Day 29 and Day 50

  2. 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.

    Measured: Day 1

  3. 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.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2021
  2. Study start23 Nov 2021 (estimated)
  3. Primary completion2 Aug 2022 (estimated)
  4. Study completion2 Aug 2022 (estimated)

Why it stopped: Study start up timelines delayed into late autumn, and with COVID cases rising in the UK, the feasibility of successfully recruiting the study and ethical concerns about starting a study that AZ may not be able to complete.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04890548
Sponsor's protocol ID
D8330C00002
Status last verified
Dec 2021
First submitted
13 May 2021
Last updated
17 Dec 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD3427 in people with Heart Failure, run by AstraZeneca.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum change from baseline in absolute forearm blood flow in the infused arm during AZD3427 IA infusions (time frame: Day 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04890548.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2021.

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