BI 690517 for Heart failure

Inclusion criteria

• {"criterion_text":"- At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years.\n- Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.\n- 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.\n- 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).\n- 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.\n- Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1.\n- 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.\n- Treated according to best possible SOC (disregarding SGLT2is and MRAs) in accordance with applicable HF local/international guidelines and judgment of the investigator.\n- Further inclusion criteria may apply in line with the Clinical Trial Protocol."}

Exclusion criteria

• {"criterion_text":"- 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\n- Further exclusion criteria may apply in line with the Clinical Trial Protocol.\n- 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.\n- 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\n- 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).\n- Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD.\n- 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.\n- Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1and until Visit 2.\n- 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.\n- Percutaneous coronary intervention (PCI, scheduled or unscheduled) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time-to-event composite: time to first cardiovascular (CV) death, first hospitalisation for heart failure (HHF) or first urgent heart-failure visit; CV death includes death of undetermined cause."}

Secondary endpoints

• {"endpoint_text":"- Time to first event of CV death or HHF.","definition_or_measurement_approach":"Time-to-event endpoint measuring time until first CV death or first hospitalisation for heart failure (HHF)."}
• {"endpoint_text":"- Occurrence of HHFs (first and recurrent).","definition_or_measurement_approach":"Counting of HHF events including first and recurrent hospitalisations for heart failure."}
• {"endpoint_text":"- Absolute change from baseline in KCCQ-TSS at Week 32.","definition_or_measurement_approach":"Change from baseline in Kansas City Cardiomyopathy Questionnaire - Total Symptom Score (KCCQ-TSS) measured at Week 32."}

Methods

• Online advertising (banner ads, social media) targeting potential participants (patient-facing channels) — country-specific translated versions documented (e.g., Spain, Poland, Germany, Netherlands, Belgium, Czechia, Italy, Romania, Bulgaria, Slovenia).
• Patient-facing printed materials: patient brochure, patient flyer, patient poster for distribution at sites and patient organisations.
• Physician referral letters and HCP fact sheets to recruit via primary and secondary care/referral pathways.
• Patient advocacy group engagement (Patient Advocacy Group Letter) to reach patient communities.
• Pre-screening website / patient pre-screening online content to allow preliminary eligibility checks.
• ePR / Participant Journey Emails (electronic participant recruitment / engagement emails) to enrolled or interested participants.
• Participant Portal content (pre-enrolment and in-trial content) to inform and retain participants.
• Referral Hub content to support site referrals and recruitment coordination.
• Country-specific recruitment materials and translated ICF/eConsent materials — multiple localized versions documented for each participating country.

Hungary

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

17-09-2024

Processing Time Days

54

Number Of Participants

331

Slovenia

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

25-11-2024

Processing Time Days

61

Number Of Participants

1

Netherlands

Earliest CTIS Part Ii Submission Date

11-09-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

12

Number Of Participants

73

Bulgaria

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

24-09-2024

Processing Time Days

103

Number Of Participants

348

Spain

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

4

Number Of Participants

250

Romania

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

102

Number Of Participants

159

Italy

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

12-09-2024

Processing Time Days

91

Number Of Participants

41

Germany

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

54

Number Of Participants

340

Poland

Earliest CTIS Part Ii Submission Date

19-08-2024

Latest Decision Or Authorization Date

22-09-2024

Processing Time Days

34

Number Of Participants

525

Belgium

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

12-09-2024

Processing Time Days

21

Number Of Participants

23

Czechia

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

33

Number Of Participants

316

Primary sponsor

Full Name

Boehringer Ingelheim International GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

IQVIA Limited

Responsibilities

Multiple operational responsibilities including eConsent, eCOA, Global Patient and Site Solutions and other listed codes

Name

Eurofins Viracor Biopharma Services LLC

Responsibilities

Laboratory testing services (sponsorDuties code 4)

Name

Labcorp Central Laboratory Services LP / Labcorp Central Laboratory Services SARL

Responsibilities

Central laboratory services, biobanking (codes include 4 and 15)

Name

Nuvisan GmbH

Responsibilities

Laboratory/other support (sponsorDuties code 4)

Name

Velocity Clinical Research Germany GmbH

Responsibilities

Clinical research / site support (listed among third parties)

Third parties

• {"country":"United States","full_name":"Eurofins Viracor Biopharma Services LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Inotiv Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Esoterix Endocrinology","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"CHU Toulouse-Laboratorie de Virologie-Institute Federatif de Biologie","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Boehringer Ingelheim Pharma GmbH & Co. KG","duties_or_roles":"Other - Biobanking DNA (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,11,12,15 (eConsent, eCOA, Global Patient and Site Solutions),2,3,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Geneva Biorepository","duties_or_roles":"Biobanking (code 15)","organisation_type":"Health care"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Other - BIOBANKING SAMPLES SERUM, PLASMA FROM EUROPE and AFRICA (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Eurofins Genomics Europe Applied Genomics GmbH","duties_or_roles":"SM07 BIOBANKING DNA (code 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Labcorp","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}