A Phase Ib Study of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment (AURORA)

Phase Ib Randomised, Placebo-controlled, Double-blind, Multicentre Study to Assess the Effects and Safety of AZD5462 on Top of Dapagliflozin in Participants With Heart Failure and Moderate Renal Impairment

A study to investigate the effects and safety of AZD5462 on top of dapagliflozin in participants with heart failure and moderate renal impairment.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Renal Impairment
• Intervention / Treatment: Drug: AZD5462; Drug: Dapagliflozin; Other: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled Phase 1b study to evaluate the safety, pharmacodynamics, and pharmacokinetics of AZD5462 on top of dapagliflozin in participants with heart failure and renal impairment.

The study will include 5 periods and approximately 9 study site visits:

• Screening Period of up to 4 weeks (at least one study visit)
• Run-in Period of up to 4 weeks (one study visit)
• Inpatient Treatment Period of 4 days (one study visit)
• Outpatient Treatment Period of up to 4 weeks (three study visits)
• Follow-up Period of up to 4 weeks (three study visits)

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a pre-existing diagnosis of heart failure (HF).
• Participants must have a left ventricular ejection fraction (LVEF) of ≤ 40% based on echocardiography taken within the last 9 months.
• Participants must have an estimated glomerular filtration rate (eGFR) of 30 to 60 milliliters per minute per 1.73 meters squared (mL/min/1.73 m2) (inclusive) at Screening as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 (creatinine) equation.
• Participants must be on stable HF standard of care (SoC) medication for at least 4 weeks prior to Screening. If the participant is currently taking diuretics, then diuretics must also be stable for at least one week prior to Screening.
• Participants must be on stable Sodium-glucose co-transporter-2 inhibitors (SGLT2) inhibitor treatment for at least 12 weeks prior to Screening.
• Minimum BMI of 18 kilograms per meter squared (kg/m2) at Screening.

Exclusion Criteria:

• Historical or current evidence of a clinically significant disease or disorder.
• Participants with a known hypersensitivity to AZD5462 or dapagliflozin, or to any of the excipients of these drug products.
• Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication.
• Cardiac ventricular arrhythmia that requires treatment. However, participants with atrial fibrillation or flutter and controlled ventricular rate (eg, resting heart rate < 110 beats per minute) are permitted. Participants with cardiac ventricular arrhythmia that are treated with antiarrhythmic agents (eg, amiodarone) and are stable are permitted.
• History of or anticipated heart transplant.
• Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, valve repair/replacement, aortic aneurysm surgery).
• Any evidence of clinically important disease or disorder which in the Investigator's opinion makes it undesirable for the participant to participate in the study.
• Positive hepatitis C antibody, hepatitis B virus surface antigen, or hepatitis B virus core antibody at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AZD5462 + dapagliflozin; Participants will receive AZD5462 on top of dapagliflozin once daily.	Drug: AZD5462; Participants will receive AZD5462 on top of dapagliflozin once daily.; Drug: Dapagliflozin; Participants will receive dapagliflozin once daily with AZD5462 or placebo.
Placebo Comparator: Placebo + dapagliflozin; Participants will receive placebo on top of dapagliflozin once daily.	Drug: Dapagliflozin; Participants will receive dapagliflozin once daily with AZD5462 or placebo.; Other: Placebo; Participants will receive placebo on top of dapagliflozin once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sodium excretion	To evaluate the effect of AZD5462 on top of dapagliflozin in participants with heart failure (HF) and renal impairment.	From Baseline to Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urine albumin-creatinine ratio (uACR)	To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment.	From Baseline to Day 1 and 29
Change in haematocrit	To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment.	From Baseline to Day 29
Number of adverse events (AEs) and Serious Adverse Events (SAEs)	To evaluate the effect of AZD5462 on top of dapagliflozin in participants with HF and renal impairment.	From Baseline to Day 57

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Actual): May 29, 2025
• Study Completion (Actual): May 29, 2025

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Renal impairment; Estimated glomerular filtration rate; Relaxin family peptide receptor 1 agonist
• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Heart Failure; Renal Insufficiency; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; dapagliflozin
• Other Study ID Numbers: D9090C00007; 2024-513142-11-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. 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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No