AZD3427 Effects on Renal Perfusion in Heart Failure Patients With Reduced Ejection Fraction and Renal Impairment

NCT06611423 | Terminated Phase 1

• 1 other identifier: D8330C00004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The present study is designed to test the effect of AZD3427 on renal perfusion in participants with heart failure and reduced eGFR (30 to 90 mL/min/1.73m2).

Conditions

Heart Failure With Reduced Ejection Fraction (HFrEF); Renal Impairment

Keywords

Heart failure with reduced ejection fraction; HFrEF; Renal impairment; Reduced eGFR; AZD3427; PET

Outcome Measures

Primary Outcomes (1)

• The volumetric fraction (%) of the renal cortex with increased perfusion from baseline to Day 8, compared to placebo.

  A PET image analysis of renal cortex measures the perfusion in approximately 8000 voxels. The volumetric fraction (%) is the fraction of voxels (%) with a positive change, i.e. increased perfusion.

  Baseline to Day 8

Secondary Outcomes (3)

• Number of participants with adverse events (AEs)

  Baseline to Day 56

• Number of participants with abnormal vital signs

  Baseline to Day 56

• Number of participants with abnormal laboratory tests results

  Baseline to Day 56

Study Arms (4)

IV Saline placebo followed by SC AZD3427

EXPERIMENTAL

Participants will receive IV administration of saline only placebo prior to a PET examination. This is followed by a single SC dose of AZD3427 on Day 1 (V2).

Biological: AZD3427; Other: Radiolabelled ligand; Other: Saline

IV Saline placebo followed by SC AZD3427 placebo

PLACEBO COMPARATOR

Participants will receive IV administration of saline only placebo prior to a PET examination. This is followed by a single SC dose of AZD3427 Placebo on Day 1 (V2).

Other: AZD3427 Placebo; Other: Radiolabelled ligand; Other: Saline

IV Dopamine diluted in saline followed by SC AZD3427

EXPERIMENTAL

Participants will receive IV administration of dopamine diluted in saline prior to a PET examination. This is followed by a single SC dose of AZD3427 on Day 1 (V2)

Biological: AZD3427; Drug: Dopamine; Other: Radiolabelled ligand

IV Dopamine diluted in saline followed by SC AZD3427 placebo

PLACEBO COMPARATOR

Participants will receive IV administration of dopamine diluted in saline prior to a PET examination. This is followed by a single SC dose of AZD3427 Placebo on Day 1 (V2).

Other: AZD3427 Placebo; Drug: Dopamine; Other: Radiolabelled ligand

Interventions

AZD3427 BIOLOGICAL

AZD3427 SC injection to be prepared using AZD3427 diluent

IV Dopamine diluted in saline followed by SC AZD3427; IV Saline placebo followed by SC AZD3427

AZD3427 Placebo OTHER

AZD3427 Placebo

IV Dopamine diluted in saline followed by SC AZD3427 placebo; IV Saline placebo followed by SC AZD3427 placebo

Dopamine DRUG

Dopamine Hydrochloride 50mg/5mL

IV Dopamine diluted in saline followed by SC AZD3427; IV Dopamine diluted in saline followed by SC AZD3427 placebo

Radiolabelled ligand OTHER

Injection of radioligand for PET examinations

IV Dopamine diluted in saline followed by SC AZD3427; IV Dopamine diluted in saline followed by SC AZD3427 placebo; IV Saline placebo followed by SC AZD3427; IV Saline placebo followed by SC AZD3427 placebo

Saline OTHER

Saline solution

IV Saline placebo followed by SC AZD3427; IV Saline placebo followed by SC AZD3427 placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AGE:
• \- Participant must be \> 20 years-old at the time of signing the informed consent.
• DISEASE CHARACTERISTICS:
• Participant must have suitable veins for cannulation.
• Participants must have a known clinical diagnosis of HF NYHA I to III for at least 12 months.
• Participants must be on stable HF standard of care medication for at least 4 weeks prior to screening, with no significant dose change or new medications added during that period. If the participant is currently taking diuretics, then diuretics must also be stable for at least 4 weeks prior to screening. It is also expected that there will be no change in treatment between screening (Visit 1) and Visit 3 in terms of drugs known to affect renal haemodynamics, including but not limited to: ACE-Is, angiotensin II receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, cyclooxygenase inhibitors, endothelin receptors antagonists, phosphodiesterase inhibitors, SGLT2is, and diuretics.
• Participants must have a left ventricular ejection fraction of ≤ 40% based on echocardiography conducted within the last 6 months.
• Participants must have an eGFR of 30 to 90 mL/min/1.73 m2 (inclusive) assessed by the CKD-EPI, 2021 (creatinine only) equation without including race (Inker et al 2021) at screening.
• BMI AND WEIGHT:
• \- Participants must have a minimum BMI of 18.0 kg/m2 and a minimum body weight of 50 kg at screening.
• SEX AND CONTRACEPTIVE REQUIREMENTS:
• For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening by one of the following:
• Postmenopausal, defined as amenorrhoea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with FSH levels in the postmenopausal range.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilisation.
• All male participants should refrain from fathering a child or donating sperm until 3 months after dosing. The female partner has to be either of non-childbearing potential or has to use a highly effective contraception form of birth control until 3 months after dosing. The female partner should be stable on their chosen method of birth control for at least 3 months prior to dosing.

You may not qualify if:

• MEDICAL CONDITIONS:
• 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.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of screening or planned surgical or other procedure before study completion.
• Clinically significant, as judged by the investigator, ventricular arrhythmias requiring pharmacological treatment.
• Historical or current evidence of a clinically significant disease or disorder including, but not limited to:
• Myocardial infarction, stroke, transient ischaemic attack, coronary artery bypass grafting, percutaneous coronary intervention, implantable cardioverter defibrillator implantation, within 12 weeks prior to screening.
• Primary cardiomyopathy other than dilated, including but not limited to sarcoidosis, amyloidosis, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, complex congenital heart disease.
• Decompensated HF or hospitalisation due to any cause \< 4 weeks prior to screening.
• Severe heart valve disease.
• Diagnosis of polycystic kidney disease or anatomical causes of chronic kidney disease.
• One kidney, renal artery stenosis, or glomerulonephritis.
• Anticipated dialysis or renal transplantation within 1 year.
• Condition where vasodilatory therapy maybe contraindicated for example but not limited to severe aortic stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy.
• History of active malignancy within 2 years, with the exception of fully excised or treated basal cell carcinoma or ≤ 2 squamous cell carcinomas of the skin.
• Participants who are under investigation for breast or cervical cancer, including participants with a pap smear of ≥ 3. All investigations must be resolved as negative for breast and cervical cancer at least 12 weeks before screening.

Sponsors & Collaborators

• AstraZeneca: lead
• CTC Clinical Trial Consultants AB: collaborator
• Karolinska Institutet: collaborator

Study Sites (1)

Research Site

Solna, 171 64, Sweden

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Dopamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Kaveh Azizi, MD

  Clinical Trial Consultants

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: September 25, 2024
• Study Start: October 15, 2024
• Primary Completion: August 21, 2025
• Study Completion: August 21, 2025
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• 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 rerefer 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.

Locations

SE (1)