Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity
Phase 3 – large-scale trial before approval
Conditions:
Heart Failure With Preserved Ejection Fraction
Heart Failure With Mildly Reduced Ejection Fraction
Obesity
Sponsor: Amgen
trial.available_in:
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Overview
This trial will examine if maridebart cafraglutide as an adjunct to standard of care will lead to a reduction in heart failure (HF) events such as HF hospitalizations and urgent HF visits, cardiovascular (CV) deaths and improvement in HF symptoms in participants with HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF) who are obese. This is a phase 3, global, multicenter, 2-part trial with a double-blind period and an open-label extension (OLE). The trial is event-driven, and Part 1 will conclude when approximately 850 primary endpoint events have occurred.
Who can participate
Inclusion Criteria:
* Age ≥ 18 years at the time of informed consent.
* BMI ≥ 30.0 kg/m\^2 at the time of randomization.
* HF diagnosed for at least 30 days with New York Heart Association (NYHA) Class II-IV at the time of informed consent.
* Managed with HF standard of care therapies.
* Left ventricular ejection fraction (LVEF) of \> 40% within 12 months from the beginning of screening.
* Elevated NT-proBNP.
* Participants must have at least one of the following:
1. Structural heart disease within 12 months prior to screening OR
2. Documented hospitalization with a primary diagnosis of decompensated HF which required IV loop diuretic treatment \> 30 days and \< 12 months prior to randomization OR
3. Evidence of elevated filling pressures within 12 months before randomization.
Exclusion Criteria:
* History of any of the following within 60 days prior to or during screening: Type I (spontaneous) MI, valvular replacement or repair, coronary revascularization, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke.
* HF due to: hypertrophic cardiomyopathy, infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, arrhythmogenic right ventricular or left ventricular cardiomyopathy/dysplasia, uncorrected primary valvular heart disease, clinically significant congenital heart disease.
* Any lifetime history of LVEF ≤ 40%.
* Hospitalized with acute decompensated HF at the time of or during the screening period.
* Type 1 diabetes mellitus, or any type of diabetes with the exception of T2DM or history of gestational diabetes.
* For participants with a prior diagnosis of T2DM (including those diagnosed during screening):
1. HbA1c \> 10.0% (86 mmol/mol) at screening
2. Uncontrolled diabetes requiring immediate therapy
3. History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization
4. One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness
5. History or presence of either proliferative diabetic retinopathy, or diabetic maculopathy, or severe non-proliferative diabetic retinopathy; or currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema.
* SBP ≥ 180 mmHg during the screening period, or on three or more blood pressure-lowering drugs with a SBP \> 160 mmHg during the screening period.
* History of chronic pancreatitis or acute pancreatitis in the 180 days before screening or during the screening period.
* Any personal lifetime history of, or family history(first-degree relative\[s\]) of medullary thyroid carcinoma or MEN-2.
* eGFR \< 20 mL/min/1.73 m\^2 (CKD-EPI creatinine (Cr)-cystatin C equation) or receiving dialysis at screening.
* Calcitonin ≥ 50 ng/L (pg/mL) at screening.
* Acute or chronic hepatitis.
* Any of the following psychiatric history:
1. History of unstable major depressive disorder or other severe psychiatric disorder within 2 years prior to screening or during the screening period
2. Lifetime history of suicide attempt
3. History of non-suicidal self-injury within 5 years prior to screening or during the screening period.
* History of any other condition that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the trial.
* Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days prior to or during the screening period or planned use during the conduct of the trial.
Interventions
Maridebart cafraglutide
DRUG
Placebo
DRUG
Locations
596
Argentina (23)
Imoba Investigaciones medicas
CABA , Buenos Aires
Centro de Investigaciones Metabolicas Cinme
CABA , Buenos Aires
Cemedic Centro de Especialidades Medicas
CABA , Buenos Aires
Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
CABA , Buenos Aires
Fundacion Respirar - Consultorios Medicos Dr Doreski
CABA , Buenos Aires
Cemic - Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno
CABA , Buenos Aires
Cardiología Palermo
Ciudad Autonoma de Buenos Aires , Buenos Aires
Ciprec Centro de Investigacion y Prevencion Cardiovascular
Ciudad Autonoma de Buenos Aires , Buenos Aires
Mautalen Salud e Investigacion Expertia SA-Osteo
Ciudad Autonoma de Buenos Aires , Buenos Aires
Instituto Medico Damic
Córdoba
Ciad - Consultorio Integral de Atencion al Diabetico
Morón , Buenos Aires
Dim Clinica Privada
Ramos Meija , Buenos Aires
Instituto de Investigaciones Clínicas Rosario-Sanatorio Delta
Rosario , Santa Fe Province
Instituto CAICI - Centro de Asistencia e Investigacion Clinica Integral
Rosario , Santa Fe Province
INECO Neurociencias Oronio
Rosario
Centro Modelo de Cardiologia
San Miguel de Tucumán , Tucumán Province
Investigaciones Clinicas Tucuman
San Miguel de Tucumán , Tucumán Province
Go Centro Medico San Nicolas
San Nicolás de los Arroyos , Buenos Aires
Instituto de Investigaciones Clinicas de San Nicolas
San Nicolás de los Arroyos , Buenos Aires
Hospital Dr Jose Maria Cullen
Santa Fe
Centro de Investigaciones Clinicas del Litoral
Santa Fe
Clinica Fusavim Privada SRL
Villa María , Córdoba Province
Instituto de Investigaciones Clinicas Zarate
Zárate
Australia (16)
Advara HeartCare Wesley
Auchenflower , Queensland
Flinders Medical Centre
Bedford Park , South Australia
Sunshine Coast University Hospital
Birtinya , Queensland
Victorian Heart Hospital
Clayton , Victoria
Canberra Hospital
Garran , Australian Capital Territory
Royal Brisbane and Womens Hospital
Herston , Queensland
Advara HeartCare Joondalup
Joondalup , Western Australia
Advara HeartCare Leabrook
Leabrook , South Australia
Sydney Cardiometabolic Centre
Liverpool , New South Wales
The Alfred Hospital
Melbourne , Victoria
Core Research Group Pty Ltd
Milton , Queensland
Advara HeartCare Mulgrave
Mulgrave , Victoria
Fiona Stanley Hospital
Murdoch , Western Australia
Gold Coast Hospital and Health Service
Southport , Queensland
Royal North Shore Hospital
St Leonards , New South Wales
Dr Heart Pty Ltd
Woolloongabba , Queensland
Austria (11)
Krankenhaus Sankt Josef Braunau
Braunau am Inn
Pro Kompetenzzentrum fuer Gesundheit
Graz
Medizinische Universitaet Graz
Graz
Klinikum Klagenfurt am Woerthersee
Klagenfurt
Ordensklinikum Linz Elisabethinen
Linz
Landeskrankenhaus Salzburg
Salzburg
Universitaetsklinikum Sankt Poelten
Sankt Pölten
Universitaetsklinikum Allgemeines Krankenhaus Wien
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