Maridebart cafraglutide for people with obesity and preserved or mildly reduced ejection fraction heart failure

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a global, phase 3, randomized, double-blind, placebo-controlled, 2-part trial with an open-label extension that enrolls adults with obesity and heart failure with preserved or mildly reduced ejection fraction. Participants are randomized to maridebart cafraglutide or placebo on top of standard-of-care therapies, and the trial is event-driven with Part 1 ending after about 850 primary endpoint events. Key outcomes include heart-failure hospitalizations and urgent heart-failure visits, cardiovascular death, and changes in heart-failure symptoms. Eligibility requires obesity (BMI ≥30), elevated NT-proBNP, LVEF >40%, and evidence of structural heart disease, recent decompensation, or elevated filling pressures.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Age ≥ 18 years at the time of informed consent.
* BMI ≥ 30.0 kg/m\^2 at 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 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 or chronic myocarditis, constrictive pericarditis, cardiac tamponade, arrhythmogenic right ventricular or left ventricular cardiomyopathy/dysplasia, uncorrected primary valvular heart disease, clinically significant congenital heart disease.
* 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 (including day 1 prior to randomization).
* 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.

Where it's running

• University of Alabama Saint Vincent's Birmingham
  Birmingham, Alabama, United States Recruiting
• SEC Clinical Research
  Dothan, Alabama, United States Recruiting
• Eastern Shore Research Institute
  Fairhope, Alabama, United States Recruiting
• Huntsville Clinical Research, LLC
  Huntsville, Alabama, United States Recruiting
• Medical Advancement Centers of Arizona
  Phoenix, Arizona, United States Recruiting
• Pima Heart and Vascular Clinical Research
  Tucson, Arizona, United States Recruiting

+636 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Amgen Call Center
• Email: medinfo@amgen.com
• Phone: 866-572-6436

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.