Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Ob
Study Description
Eligibility
- Age greater than or equal to 18 years.
- BMI greater than or equal to 30 kg/m^2.
- 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 greater than 40%.
- Elevated NT-proBNP.
- Participants must have at least one of the following:
a. Structural heart disease OR
b. Documented hospitalization with a primary diagnosis of decompensated HF within 12 months before randomization OR
c. 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 less than or equal to 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:
a. HbA1c greater than 10.0%
b. Uncontrolled diabetes requiring immediate therapy
c. History of diabetic ketoacidosis or hyperosmolar state/coma
d. One or more episodes of severe hypoglycemia within 6 months before screening and/or history of hypoglycemia unawareness
e. History of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy.
- SBP greater than or equal to 180 mmHg , or on three or more blood pressure-lowering drugs with a SBP greater than 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 less than 20 mL/min/1.73 m^2 (CKD-EPI creatinine (Cr)-cystatin C equation) or receiving dialysis at screening.
- Calcitonin greater than or equal to 50 ng/L (pg/mL) at screening.
- Acute or chronic hepatitis.
- Any of the following psychiatric history:
a. History of unstable major depressive disorder or other severe psychiatric disorder within 2 years before screening
b. Lifetime history of suicide attempt
c. 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.
