A study to test whether vicadrostat (BI 690517) in combination with empagliflozin helps people with heart failure.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Oct 2024 → ongoing

Decision date (initial)

2024-09-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Boehringer Ingelheim International GmbH

External identifiers

EU CT number

2023-509706-30-00

WHO UTN

U1111-1302-4422

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Safety

The primary objective is to demonstrate the superiority of the combination of vicadrostat [...] and empagliflozin [...] compared with placebo and empagliflozin [...] for the time to first CV death, HHF or urgent HF visit in participants with HF and LVEF ≥40%.

Secondary objectives 3

1. To demonstrate the superiority of the combination of vicadrostat […] and empagliflozin […] to placebo and empagliflozin […] for the time to first event of CV death or HHF, the total number of HHF (first and recurrent) and the absolute change from baseline in KCCQ-TSS at Week 32.
2. To demonstrate the superiority of the combination of vicadrostat […] and empagliflozin […] to placebo and empagliflozin […] for the time to first event of CV death or the total number of HHF (first and recurrent), the absolute change from baseline in KCCQ-TSS at Week 32, the time to CV death and the time to all-cause mortality.
3. To evaluate the combination of vicadrostat [...] and empagliflozin [...] compared with placebo and empagliflozin [...] for the time to first HHF, time to first occurrence of the composite renal endpoint, as well as the absolute change from baseline in KCCQ-CSS at Week 32, in KCCQ-TSS at Week 52, and in KCCQ-OSS at Week 32 and 52. Furthermore, the absolute change from baseline in systolic blood pressure (SBP) at Week 32 in participants with baseline SBP ≥130 mmHg and absolute change from baseline in diastolic blood pressure (DBP) at Week 32 in participants with baseline DBP ≥80 mmHg will be assessed.

Conditions and MedDRA coding

Heart failure (HF)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years.
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
3. Male or female participants. Women of childbearing potential must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.
4. Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA class II-IV at Visit 1, with LVEF ≥40% per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI, or CT). A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before randomisation at Visit 2 (if several values are available, the most recent one should be considered).
5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement). Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit 2. If several values are available, the most recent one should be considered.
6. Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1.
7. At least one of the following: a) Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1 b) Documented hospitalisation for HF within 6 months prior to Visit 1 c) Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1 a. in participants without Afib or Aflutter (at Visit 1 ECG): ≥900 pg/mL b. for participants with Afib or Aflutter (at Visit 1 ECG): ≥1800 pg/mL d) UACR ≥30 mg/g, analysed at the central laboratory at Visit 1.
8. Treated according to best possible SOC (disregarding SGLT2is and MRAs) in accordance with applicable HF local/international guidelines and judgment of the investigator.
9. Further inclusion criteria may apply in line with the Clinical Trial Protocol.

Exclusion criteria 10

1. Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with MRA should not be interrupted with the intention of enrolment into the study
2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator.
3. Receiving the following treatments: a. a direct renin inhibitor (e.g. aliskiren) at Visit 2 b. more than one ACEI, ARB or ARNI, used simultaneously at Visit 2 c. In case of acute decompensated HF i. i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), or i.v. natriuretic peptide (e.g., nesiritide, carperitide), or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), within 24 hours prior to randomisation (Visit 2) ii. i.v. diuretic with a dose that has been increased/intensified within 6 hours prior to randomisation (a stable dose of an i.v. diuretic is not exclusionary) d. Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2 e. Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial
4. MI, TIA, stroke, coronary artery bypass graft surgery/CABG, heart valve surgery/intervention or any other major surgery (major according to the investigator’s assessment) within 90 days prior to Visit 2,or scheduled for major elective surgery (e.g. hip replacement, CABG).
5. Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD.
6. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or genetic hypertrophic cardiomyopathy, known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2.
7. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1and until Visit 2.
8. Known severe valvular heart disease (obstructive or regurgitant), as per investigator’s judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study.
9. Percutaneous coronary intervention (PCI, scheduled or unscheduled) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2.
10. Further exclusion criteria may apply in line with the Clinical Trial Protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The composite primary endpoint is the time to first event of CV death, HHF or urgent HF visit. CV death includes death of undetermined cause.

Secondary endpoints 3

1. Time to first event of CV death or HHF.
2. Occurrence of HHFs (first and recurrent).
3. Absolute change from baseline in KCCQ-TSS at Week 32.

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 13

Locations

11 EU/EEA countries · 207 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 525 files

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

Application history

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