Phase III study to evaluate the effect of balcinrenone/dapagliflozin in patients with heart failure and impaired kidney function

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Jul 2024 → ongoing

Decision date (initial)

2024-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-508162-15-00

ClinicalTrials.gov

NCT06307652

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic, Others

To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death and HF events with and without hospitalisation

Secondary objectives 5

1. 1. To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total occurrences of CV death, and HF events with and without hospitalisation
2. 2. To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the rate of total HF hospitalisations
3. 3. To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of CV death
4. 4. To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause, HF events, and improving patient reported symptoms of HF
5. 5. To determine whether balcinrenone/dapagliflozin is superior to dapagliflozin in reducing the risk of death from any cause

Conditions and MedDRA coding

Chronic HF and comorbid impairment of kidney function who had a recent HF event to evaluate the effect of balcinrenone/dapagliflozin versus dapagliflozin alone on HF events and cardiovascular (CV) death

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration, Pharmaceuticals And Medical Devices Agency

Plan to share 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. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Age ≥ 18 years
2. 2. Documented diagnosis of symptomatic HF (NYHA functional class II-IV)
3. 3. Having had a recent HF event within 6 months (hospitalization or urgent visit)
4. 4. Have a LVEF value from an assessment within the last 12 months
5. 5. Managed with SoC therapy for HF and renal impairment according to local guidelines
6. 6. NT-proBNP must be >300 pg/mL (>600 pg/mL if concomitant atrial fibrillation or atrial flutter)
7. 7. Not taking an MRA
8. 8. An eGFR ≥ 20 to < 60 mL/min/1.73 m2
9. 9. Serum/plasma potassium ≤ 5.0 mmol/L

Exclusion criteria 12

1. 1. Acute coronary syndrome (unstable angina or myocardial infarction), stroke or transient ischaemic attack within the previous 3 months prior to enrolment or during the screening period
2. 10. Acute or chronic liver disease with severe impairment of liver function, eg, ascites, oesophageal varices, coagulopathy, and encephalopathy
3. 11. Suspected or confirmed COVID-19 infection within the last 4 weeks or hospitalisation for COVID-19 within the last 12 weeks
4. 2. Major cardiac surgery, coronary revascularisation or valvular repair or replacement, or implantation of a Cardiac resynchronisation therapy device within 3 months prior to enrolment or planned to undergo any of these operations
5. 3. History of hypertrophic obstructive cardiomyopathy
6. 4. Complex congenital heart disease or severe uncorrected primary valvular disease
7. 5. Symptomatic bradycardia or second- or third-degree heart block without a pacemaker
8. 6. Systolic BP < 90 mmHg, or symptomatic hypotension within the past 24 hours
9. 7. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD or exacerbation of COPD requiring invasive mechanical ventilation assistance within 12 months prior to enrolment
10. 8. Type 1 diabetes mellitus
11. 9. Kidney replacement therapy in the past 4 weeks, currently requiring kidney replacement or imminent plan to start kidney replacement therapy
12. 12. Treatment with strong or moderate CYP3A4 inhibitor or inducer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first occurrence of any of the components of the composite of: • CV death • HF hospitalisation • HF event without hospitalisation

Secondary endpoints 5

1. 1. Total occurrences (first and recurrent) of the components of the composite of: • CV death • HF hospitalisation • HF event without hospitalisation
2. 2. Total occurrences (first and recurrent) of HF hospitalisations
3. 3. Time to CV death
4. 4. The hierarchical composite endpoint of death from any cause, total HF events, and change from baseline in KCCQ total symptom score to 24-week post-randomisation
5. 5.Time to death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

15 EU/EEA countries · 212 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 138 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

43 submissions — initial application plus substantial / non-substantial modifications