BI 690517 for Heart failure

Inclusion criteria

• {"criterion_text":"- At least 18 years old and at least at the legal age of consent in countries where it is greater than 18 years"}
• {"criterion_text":"- Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial"}
• {"criterion_text":"- Male or female participants. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in Section 4.2.2.3 of the protocol"}
• {"criterion_text":"- Chronic HF diagnosed at least 3 months before Visit 1, and in NYHA classes II to 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 LVEF assessments are available, the most recent one should be considered)"}
• {"criterion_text":"- Elevated NT-proBNP at Visit 1, analysed at the central laboratory a. ≥ 600 pg/mL (or if hospitalised for heart failure within the previous 12 months, ≥ 400 pg/mL) for participants without Afib or Aflutter (Visit 1 ECG2) or b. ≥ 1200 pg/mL for participants with Afib or Aflutter (Visit 1 ECG2) (irrespective of history of heart failure hospitalisation)"}
• {"criterion_text":"- Treated according to best possible SOC (disregarding SGLT2i and MRA) in accordance with applicable HF local/international guidelines and judgement of the investigator, which should in general include (unless contraindicated or not tolerated): • An ACE inhibitor, or ARB or ARNi; and • A beta-blocker; and • If considered appropriate by the patient’s treating physician, an SGLT2i (prior SGLT2i treatment will be replaced by the study drug at randomisation)"}

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 an MRA should not be discontinued with the intention of study enrolment."}
• {"criterion_text":"- Лечение с амилорид или друг калий-съхраняващ диуретик в рамките на 14 дни преди визита 1 или нужда от такова лечение преди рандомизирането или планирано такова лечение по време на изпитването по преценка на изследователя."}
• {"criterion_text":"- Receiving the following treatments: • A direct renin inhibitor (e.g. aliskiren) at Visit 2 • More than one ACEi, ARB or ARNi used simultaneously at Visit 2 • Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial • Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2 • In case of acute decompensated HF: o i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), or i.v. natriuretic peptide (e.g. nesiritide, carperitide), or mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device) within 24 hours prior to randomisation o 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)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Percutaneous coronary intervention (PCI) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2"}
• {"criterion_text":"- Heart transplant recipient, awaiting heart transplant, or currently implanted LVAD"}
• {"criterion_text":"- Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within 12 months prior to Visit 1 and until Visit 2"}
• {"criterion_text":"- Acute inflammatory heart disease, such as acute myocarditis, within 90 days preceding prior to Visit 1 and until Visit 2"}

Primary endpoints

• {"endpoint_text":"- The composite primary endpoint addressing the primary objective is as follows: Time to first event of • Cardiovascular (CV) death; or • Hospitalisation for heart failure (HHF); or • Urgent heart failure (HF) visit","definition_or_measurement_approach":"Time to first occurrence of any of: CV death, hospitalisation for heart failure (HHF), or urgent HF visit; analysed as time-to-event (comparison of combination vicadrostat+empagliflozin vs placebo+empagliflozin)."}

Secondary endpoints

• {"endpoint_text":"- Time to first event of cardiovascular death or hospitalisation for heart failure","definition_or_measurement_approach":"Time-to-event analysis for composite of CV death or HHF."}
• {"endpoint_text":"- Occurrences of hospitalisation for heart failure (first and recurrent)","definition_or_measurement_approach":"Count of first and recurrent HHF events (total number of HHF per participant)."}
• {"endpoint_text":"- Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 32","definition_or_measurement_approach":"Change from baseline in KCCQ-TSS measured at Week 32 using the KCCQ instrument administered centrally (eCOA)."}

Other endpoints

• {"endpoint_text":"- Time to first HHF","definition_or_measurement_approach":"Time-to-event for first hospitalisation for heart failure."}
• {"endpoint_text":"- Time to first occurrence of the composite renal endpoint","definition_or_measurement_approach":"Time-to-event for predefined composite renal outcome (definition in protocol)."}
• {"endpoint_text":"- Absolute change from baseline in KCCQ-Clinical Summary Score (KCCQ-CSS) at Week 32","definition_or_measurement_approach":"Change from baseline in KCCQ-CSS at Week 32."}
• {"endpoint_text":"- Absolute change from baseline in KCCQ-TSS at Week 52","definition_or_measurement_approach":"Change from baseline in KCCQ-TSS at Week 52."}
• {"endpoint_text":"- Absolute change from baseline in KCCQ-Overall Summary Score (KCCQ-OSS) at Week 32","definition_or_measurement_approach":"Change from baseline in KCCQ-OSS at Week 32."}
• {"endpoint_text":"- Absolute change from baseline in KCCQ-Overall Summary Score (KCCQ-OSS) at Week 52","definition_or_measurement_approach":"Change from baseline in KCCQ-OSS at Week 52."}
• {"endpoint_text":"- Absolute change from baseline in systolic blood pressure (SBP) at Week 32 in participants with baseline SBP ≥ 130 mmHg","definition_or_measurement_approach":"Change from baseline in SBP at Week 32 in specified baseline SBP subgroup."}
• {"endpoint_text":"- Absolute change from baseline in diastolic blood pressure (DBP) at Week 32 in participants with baseline DBP ≥ 80 mmHg","definition_or_measurement_approach":"Change from baseline in DBP at Week 32 in specified baseline DBP subgroup."}

Methods

• Doctor-to-Patient letters distributed via HCPs to inform potential patients and request referral (site-mediated physician outreach).
• Banner advertisements and online ads (paid banner ads) targeting patients (digital channels/social media) as per country recruitment packs.
• Unpaid social media ads and posts (organic social media) targeted to potential participants.
• Patient brochures, flyers and posters distributed at trial sites and via advocacy channels for patient-facing recruitment.
• Patient portal content and a pre-screening website / referral hub for online pre-screening and information.
• Physician referral letters and HCP fact sheets to engage healthcare professionals and facilitate referrals.
• Patient Advocacy Group outreach (Patient Advocacy Group Letters) to support community engagement.
• eConsent materials including video storyboards, glossaries and participant-facing screenshots to support remote consent and onboarding.

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 CRO/operational responsibilities including eConsent, eCOA, global patient and site solutions, project management (codes listed in CTIS thirdParties)

Name

Signant Health Global LLC

Responsibilities

eCOA / patient-facing electronic data capture

Name

Velocity Clinical Research (and other listed clinical research organisations in trial sites and third parties)

Responsibilities

Clinical research site network / site management (as listed in thirdParties and trial documents)

Third parties

• {"country":"France","full_name":"Centre Hospitalier Universitaire De Toulouse","duties_or_roles":"Sponsor duties code 4 (as listed)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company / eCOA vendor"}
• {"country":"Germany","full_name":"Eurofins Genomics Europe Applied Genomics GmbH","duties_or_roles":"Biobanking DNA","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple sponsor duties including project management, eConsent, eCOA, Global Patient and Site Solutions (codes 1,11,12,15 etc as listed)","organisation_type":"Pharmaceutical company / CRO"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Central laboratory / biorepository (code 4)","organisation_type":"Pharmaceutical company / Laboratory"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central laboratory / biorepository (code 4)","organisation_type":"Pharmaceutical company / Laboratory"}
• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"Sponsor duties (code 4)","organisation_type":"Pharmaceutical company / Laboratory"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL (Biobanking samples serum, plasma from Europe and Africa)","duties_or_roles":"Biobanking samples serum, plasma from Europe and Africa (code 15)","organisation_type":"Pharmaceutical company / Laboratory"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Biobanking samples serum, plasma from Rest of the World (code 15)","organisation_type":"Pharmaceutical company / Laboratory"}
• {"country":"United States","full_name":"Labcorp","duties_or_roles":"Central laboratory support (code 4)","organisation_type":"Laboratory/Research/Testing facility"}