Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity

Open to people ages 18-99

• Age ≥ 18 years.
• BMI ≥ 30 kg/m².
• HF diagnosed for at least 30 days before screening with New York Heart Association (NYHA) Class II-IV.
• Managed with HF standard of care therapies.
• Left ventricular ejection fraction (LVEF) of > 40%.
• Elevated NT-proBNP.
• Participants must have at least one of the following:
  1. Structural heart disease OR
  2. Documented hospitalization with a primary diagnosis of decompensated HF within 12 months before randomization OR
  3. Evidence of elevated filling pressures within 12 months before randomization.

• History of any of the following within 60 days before 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, or uncorrected primary valvular heart disease, or clinically significant congenital heart disease.
• Any lifetime history of LVEF ≤ 40%.
• Currently hospitalized with acute decompensated HF or hospitalization with a primary diagnosis of decompensated HF within 30 days before screening.
• 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 at screening:
  1. HbA1c > 10.0%
  2. Uncontrolled diabetes requiring immediate therapy
  3. History of diabetic ketoacidosis or hyperosmolar state/coma
  4. One or more episodes of severe hypoglycemia within 6 months before screening and/or history of hypoglycemia unawareness
  5. History of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy.
• SBP ≥ 180 mmHg , or on three or more blood pressure-lowering drugs with a SBP > 160 mmHg.
• History of chronic pancreatitis or acute pancreatitis in the 180 days before screening.
• Family (or personal) history of medullary thyroid carcinoma or MEN-2.
• eGFR < 20 mL/min/1.73 m² (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 before screening
  2. Lifetime history of suicide attempt
  3. History of non-suicidal self-injury within 5 years before screening.
• History of any other condition that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the study.
• 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 before randomization or planned use during the conduct of the study.