stop_circleTerminated/Withdrawn

Chronic heart failure

A study to learn how safe study drug BAY2413555 is, how it affects the body, and how it moves into, through, and out of the body over 4 weeks of use in participants with heart failure and implanted cardiac defibrillator or cardiac resynchronization devices (ICD/CRT)

Trial purpose

Researchers are looking for a better way to treat people who have chronic heart failure. Chronic heart failure is a medical condition with shortness of breath, tiredness and ankle swelling in which the heart does not pump blood as well as it should.

BAY2413555 is a new compound which is under development for the treatment of heart failure. Heart failure is a serious disease in which the heart pumps less well. BAY2413555 is expected to protect the heart and improve cardiac function.

The main purpose of this study is to learn how safe BAY2413555 is compared to placebo in participants with chronic heart failure and implanted cardiac defibrillator, or cardiac resynchronization devices (ICD/CRT). A placebo is a treatment that looks like a medicine, but does not have any medicine in it. ICD/CRT are machines placed in the body that use an electric shock/impulse to reset the heart or get it beating correctly. To study the safety, the researchers will record all medical problems the participants may have during the study after starting the study treatment. Medical problems that happen after the participants have started their treatment are also known as “treatment emergent adverse events” (TEAEs). The TEAEs will be compared between participants who received BAY2413555 and those who received placebo.

The second purpose of this study is to learn whether BAY2413555 effects electrical signals inside the heart compared to placebo.

The study has two parts, A and B. Each part will last for two weeks. In part A, the participants will be assigned by chance to either take BAY2413555 as a tablet by mouth once per day or a placebo. Participants from part A who do not need to stop the study based on predefined criteria continue in part B. They will be assigned by chance to receive either the same dose of BAY2413555 as in part A or a higher dose. Participants who have taken placebo in part A will as well be assigned in part B.

Each participant will be in the study for approximately 90 days (including the screening period and follow-up period). In the study, participants will take study medication for 28 days. 8 visits to the study site and 1 telephone contact visit are planned. During the study, the study team will:
•   do physical examinations
•   check vital signs
•   examine heart health using ECG
•   check the participants’ ICD/CRT information
•   take exercise testing
•   take blood and urine samples
•   ask the participants questions about how they are feeling about their quality of life
•   ask the participants questions about how they are feeling and what
adverse events they are having.
An adverse event is any problem that happens during the trial. Doctors keep track of all adverse events that happen in trials, even if they do not think the adverse events might be related to the study treatments or a study procedure. Participants will be closely monitored during the entire study duration and site personnel will take action to mitigate any negative effect, if any, as appropriate.

About 30 days after the participants take their last treatment, the study doctors and their team will check the participants’ health.

Key Participants Requirements

Sex

All

Age

18 - 79 Years
  • - Providing signed informed consent
    - Diagnosis of heart failure lasting for at least 3 months, New York Heart Association (NYHA) functional class I-III prior to Visit 1
    - Left ventricular ejection fraction (LVEF) ≤ 45% as documented by any imaging modality within the past 12 months prior to Visit 1
    - Treatment with Guideline-Directed Medical Therapy Including with mandatory betablocker treatment with either Metoprolol, Carvedilol, Bisoprolol or Nebivolol on stable, highest individually tolerated dose for at least 2 weeks prior to Visit 1
    - Implanted cardiac defibrillator (ICD) with pacemaker backup function OR cardiac resynchronization device (CRT)
     -- first implantation at least 3 months prior to Visit 1
  • - Permanent atrial fibrillation or other than Sinus rhythm at Visit 1
    - History of higher degree atrioventricular (AV) block (Mobitz type II or third-degree AV block) within 4 weeks prior to Visit 1
    - Indication for or planned procedure:
     -- Planned cardiac surgery, carotid angioplasty or surgery, transcatheter aortic valve implantation (TAVI) or mitral valve clipping within 3 months starting from the Screening Visit
     -- Percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or implantation of a cardiac resynchronization therapy defibrillator device indicated at Screening or planned within 3 months starting from the Screening Visit
     -- Valvular Disease Repair indicated at Screening or planned within 3 months starting from the Screening Visit.
    - Occurrence of any of the following within 4 weeks prior to Visit 1:
     -- Myocardial infarction
     -- Stroke or transient ischemic attack (TIA)
     -- coronary artery bypass graft (CABG)
     -- percutaneous coronary intervention (PCI)
     -- Carotid angioplasty
     -- Ablation therapy of atrial fibrillation or other rhythm abnormalities
    - Heart rate (HR) > 100 bpm at Screening Visit
    - Restrictive, infiltrative or hypertrophic cardiomyopathy, constrictive pericarditis, acute myocarditis within 3 months prior to Visit 1
    - Malignancy of the hematological system within 5 years prior to the Screening Visit
    - Listed for heart transplantation and/or anticipated implantation of a ventricular assist device at the Screening Visit
    - Hepatic insufficiency classified as Child-Pugh B or C at the Screening Visit
    - Estimated (according to the investigator’s judgement) inability to perform exercise testing
    - Any of the following from the blood sample taken at the Screening Visit
     -- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 (calculated according to the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
     -- Hemoglobin < 11 g/dL
     -- White blood cell (WBC) < 3000/mm^3
     -- Thrombocytes < 100 000/mm^3
    - Currently receiving or planned to receive dialysis or ultrafiltration
    - Chronic obstructive pulmonary disease (COPD) Stage 3 or 4 (GOLD criteria), requiring treatment, or symptomatic asthma requiring current treatment
    - Prior or concomitant therapy with cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or inducers.
    Relevant substances need to be discontinued
     -- at least 2 weeks before randomization for CYP3A4 inducers
     -- at least 5 half-lives before randomization for CYP3A4 inhibitors
    Restarting of these therapies is possible 28 days after last intake of study intervention. This criterion also applies to other inhibitors of CYP3A4, e.g., grapefruit.
    Prior and concomitant therapy with amiodarone is allowed.
    - Concomitant treatment with acetylcholine esterase inhibitors within 4 weeks prior to Visit 1
    - Use of other investigational drugs. Previous (within 4 weeks, or 5 half-lives of the investigational drug, whichever is longer, prior to Visit 1) or concomitant participation in another clinical study with investigational medicinal product(s) or device(s)
    - Life expectancy < 6 months at the Screening Visit

Trial summary

Enrollment Goal
22
Trial Dates
September 2022 - March 2023
Phase
Phase 1
Could I Receive a placebo
Yes
Products
BAY2413555
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Universitätsmedizin Greifswald | Innere Medizin BGreifswald, 17489, Germany
Withdrawn
Ev. Krankenhaus Hagen-Haspe|Kardiologie und RhythmologieHagen, 58135, Germany
Withdrawn
Klinikum Singen|Kardiologie und internistische IntensivmedizSingen, 78224, Germany
Completed
Pratia | Klinische Forschung DresdenDresden, 01069, Germany
Withdrawn
Klinische Forschung Schwerin GmbHSchwerin, 19055, Germany
Withdrawn
Georg August UniGoettingen | Kardiologie und PneumologieGöttingen, 37075, Germany
Withdrawn
Golden Jubilee National HospitalClydebank, G81 4DY, United Kingdom
Withdrawn
University Hospitals Coventry and Warwickshire NHS TrustCoventry, CV2 2DX, United Kingdom
Withdrawn
Ninewells Hospital and Medical SchoolDundee, DD1 9SY, United Kingdom
Withdrawn
Hammersmith HospitalLondon, W12 0HS, United Kingdom
Withdrawn
Blackpool Victoria HospitalBlackpool, FY3 8NR, United Kingdom
Withdrawn
South Oklahoma Heart Research, LLCOklahoma City, 73135, United States
Withdrawn
University of Nebraska Medical CenterOmaha, 68105, United States
Completed
White Oak Medical CenterSilver Spring, 20904, United States
Completed
Capital Area Research, LLCCamp Hill, 17011, United States
Completed
Accel Research Sites - Atlanta Clinical Research CenterAtlanta, 30342, United States
Completed
Humanitas Research Hospital | Cardio Center - Clinical, Interventional Cardiology and Coronary CareMilano, 20089, Italy
Withdrawn
ASST Spedali Civili di BresciaBrescia, 25123, Italy
Completed
Fondazione Toscana Gabriele Monasterio | Heart Hospital Gaetano Pasquinucci - Cardiology DepartmentPisa, 56124, Italy
Withdrawn
ASST Papa Giovanni XXIIIBergamo, 24127, Italy
Withdrawn
La Fe University and Polytechnic Hospital | Unidad de Insuficiencia Cardiaca y TrasplanteValencia, 46026, Spain
Completed
Hospital del Mar | Cardiology DepartmentBarcelona, 08003, Spain
Completed
Hospital Alvaro Cunqueiro | Cardiology DepartmentBabio - Beade, 36312, Spain
Completed
Hospital General Universitario de ValenciaValencia, 46014, Spain
Completed
Hospital Universitario Virgen de la Victoria | Cardiology DepartmentMálaga, 29010, Spain
Completed
Junta de Andalucía | University Hospital Reina Sofia - Cardiology DepartmentCórdoba, 14004, Spain
Completed
Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology DepartmentBarcelona, 08907, Spain
Withdrawn
RigshospitaletKøbenhavn Ø, 2100, Denmark
Completed
Capital Region | Gentofte Hospital - Cardiology ResearchHellerup, 2900, Denmark
Completed
Zealand University Hospital | Roskilde - Cardiology DepartmentRoskilde, 4000, Denmark
Completed
Odense Universitetshospital, Hjertemedicinsk Amb.Odense C, 5000, Denmark
Withdrawn
Aarhus Universitetshospital, SkejbyAarhus N, 8200, Denmark
Withdrawn
Nemocnice Ceske Budejovice, a.s. Department of kardiologieCeske Budejovice, 370 01, Czechia
Withdrawn
Fakultni nemocnice BrnoBrno, 625 00, Czechia
Withdrawn
Ustredni vojenska nemocnice PrahaPraha 6, 169 02, Czechia
Withdrawn
Institut Klinicke a Experimentalni MedicinyPraha 4, 140 21, Czechia
Withdrawn
Vseobecna fakultni nemocnice v PrazePraha 2, 12808, Czechia
Withdrawn
Shamir Medical Center (Assaf Harofeh)Zrifin, 7030000, Israel
Completed
Rambam Health Care Campus | Internal Medicine - Cardiology DepartmentHaifa, 3109601, Israel
Completed
Barzilai Ashkelon University Medical Center | Cardiology DepartmentAshkelon, 7830604, Israel
Completed
Ziv Medical Center | Cardiology DepartmentZefat, 1311001, Israel
Withdrawn
Health Corporation of Galilee Medical CenterNahariya, 22100, Israel
Withdrawn
Shaare Zedek Medical CenterJerusalem, 9103102, Israel
Withdrawn
Duke University Medical CenterDurham, 27710, United States
Withdrawn
Medizinische Universität GrazGraz, 8036, Austria
Withdrawn
Universitätsklinikum St. PöltenSt. Pölten, 3100, Austria
Withdrawn
Medizinische Universität InnsbruckInnsbruck, 6020, Austria
Withdrawn
Imed19-privatWien, 1190, Austria
Withdrawn
UMHAT Prof. Dr Aleksandar ChirkovSofia, 1431, Bulgaria
Withdrawn
UMHAT Alexandrovska EADSofia, 1431, Bulgaria
Withdrawn
Acibadem City Clinic Multiprofile Hospital for Active TreatmSofia, 1407, Bulgaria
Withdrawn
University of Semmelweis/ Semmelweis EgyetemBudapest, 1122, Hungary
Withdrawn
Debreceni Egyetem Klinikai KozpontDebrecen, 4032, Hungary
Withdrawn
PTE KK I Belgy Klinika Klinikai Farmakologiai TanszekPecs, 7624, Hungary
Withdrawn
Hopital Europeen Georges Pompidou – Service de CardiologieParis, 75015, France
Withdrawn
Hôpital Louis Pradel - BronBRON CEDEX, 69677, France
Withdrawn
CHU de Grenoble – Service de CardiologieLa Tronche, 38700, France
Withdrawn
CHU Rennes, H Pontchaillou, CardiologieRennes, 35033, France
Withdrawn
University Hospital of WalesCardiff, CF14 4XW, United Kingdom
Withdrawn
Universitätsklinikum AKH WienWien, 1090, Austria
Withdrawn
UMHAT Sveti GeorgiPlovdiv, 4000, Bulgaria

Primary Outcome

  • Number of participants with treatment-emergent adverse events (TEAEs)
    date_rangeTime Frame:
    Up to 56 days

Secondary Outcome

  • Number of participants with higher degree atrioventricular (AV) blocks, symptomatic pauses/bradycardia
    date_rangeTime Frame:
    Up to 28 days
  • Changes from baseline in resting heart rate (HR) after 2 and 4 weeks of dosing with BAY2413555
    date_rangeTime Frame:
    Up to 28 days

Trial design

A phase 1b double-blind, randomized, placebo-controlled, multicenter, dose titration study to evaluate the safety, tolerability, and pharmacokinetics of 4 weeks treatment with BAY 2413555 in participants with heart failure and implanted cardiac defibrillator or cardiac resynchronization devices
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
3