A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Maridebart Cafraglutide on Mortality and Morbidity in Participants Living With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (MARITIME-HF)

Plain English Summary

Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity is a Phase 3 clinical trial sponsored by Amgen studying Heart Failure With Preserved Ejection Fraction, Heart Failure With Mildly Reduced Ejection Fraction, Obesity. This study tests if a new drug, maridebart cafraglutide, can help reduce heart failure events and cardiovascular deaths in people with specific types of heart failure and obesity. It is for adults aged 18 and older who have heart failure with preserved or mildly reduced ejection fraction and are obese (BMI of 30 or higher). Participants will receive either the study drug or a placebo (a dummy treatment) by injection, and will be monitored for about 35 months. Standard treatments for heart failure and obesity are available as alternatives, but this trial explores a new combination therapy. The trial aims to enroll 5056 participants.

Official Summary

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

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a diagnosis of heart failure and obesity (BMI 30+). Patients must have specific heart function measurements (LVEF > 40%) and elevated NT-proBNP levels. Individuals with recent heart attacks, strokes, major heart surgeries, or certain other heart conditions may not be eligible. Those with uncontrolled diabetes, severe kidney problems, or certain thyroid or psychiatric conditions are also excluded. This trial is studying Heart Failure With Preserved Ejection Fraction, Heart Failure With Mildly Reduced Ejection Fraction, Obesity, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures whether the study drug reduces the combined risk of cardiovascular death or heart failure hospitalizations and urgent visits, indicating its potential to improve survival The specific primary outcome measures are: Time to First Occurrence of a Composite Endpoint Consisting of: CV Death or HF Events (Up to approximately 35 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant unmet need in treating heart failure with preserved ejection fraction and obesity, aiming to improve outcomes and reduce hospitalizations. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Heart Failure With Preserved Ejection Fraction, Heart Failure With Mildly Reduced Ejection Fraction, Obesity, where improved treatment options are needed.

Investor Insight

This Phase 3 trial by Amgen targets a large patient population with heart failure and obesity, a growing concern, suggesting a significant market opportunity if the drug proves effective and safe. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 5056 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific heart condition and overall health. Participation involves regular clinic visits for injections, tests, and monitoring of your heart health and symptoms. Be prepared for a commitment of up to approximately 35 months, with potential for an open-label extension. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 5,056 participants

Interventions

• DRUG: Maridebart cafraglutide — Maridebart cafraglutide will be administered SC.
• DRUG: Placebo — Placebo will be administered SC.

Primary Outcomes

• Time to First Occurrence of a Composite Endpoint Consisting of: CV Death or HF Events (Up to approximately 35 months)

Secondary Outcomes

• Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) for Participants with Baseline KCCQ-CSS Score ≤ 80 (Baseline and Week 48)
• Change from Baseline in the KCCQ Total Symptom Score (TSS) for Participants with Baseline KCCQ-CSS Score ≤ 80 (Baseline and Week 48)
• Total Number of HF Events Including First and Recurrent HF Events (Up to approximately 35 months)
• Time to First Occurrence of a Composite Endpoint Consisting of: Myocardial Infarction (MI), Ischemic Stroke, CV Death (Major Adverse Cardiac Events [MACE]), or HF Events (Up to approximately 35 months)
• Time to First Event of a Composite Nephropathy Endpoint (Up to approximately 35 months)

Full Eligibility Criteria

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.

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• SEC Clinical Research, Dothan, Alabama, United States
• Eastern Shore Research Institute, Fairhope, Alabama, United States
• Heart Center Research LLC, Huntsville, Alabama, United States
• HonorHealth, Phoenix, Arizona, United States
• Medical Advancement Centers of Arizona, Phoenix, Arizona, United States
• Pima Heart and Vascular Clinical Research, Tucson, Arizona, United States
• Yuma Clinical Trials, Yuma, Arizona, United States
• Arkansas Cardiology, Little Rock, Arkansas, United States
• National Heart Institute, Beverly Hills, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Heart Failure with Preserved Ejection Fraction (HFpEF)
• Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)
• Obesity
• Cardiovascular Disease
• Hypertension
• Diabetes Mellitus Type 2
• Chronic Kidney Disease
• Pulmonary Hypertension
• Coronary Artery Disease
• Metabolic Syndrome

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