Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity (MARITIME-CV)

Amgen

Status and phase: Enrolling; Phase 3

Conditions: Overweight; Atherosclerotic Cardiovascular Disease; Obesity

Treatments: Drug: Maridebart Cafraglutide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07037433

20220196

Details and patient eligibility

About

The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.

Enrollment: 12,800 estimated patients

Sex: All

Ages: 45 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Age ≥ 45 years at screening.

• BMI of ≥ 27.0 kg/m^2 at screening.

• History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:

  • Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
  • Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
  • Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) < 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.

Exclusion Criteria

• History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).

• New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.

• Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.

• For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):

  • HbA1c > 10.0% (86 mmol/mol) at screening.
  • History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
  • One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
  • History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.

• 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 trial.

• History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.

• Family (first-degree relative[s]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).

• Calcitonin ≥ 50 ng/L (pg/mL) at screening.

• Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) > 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) > 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).

• History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).

• Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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12,800 participants in 2 patient groups, including a placebo group

Maridebart Cafraglutide

Experimental group

Description:

Participants will receive maridebart cafraglutide subcutaneously (SC).

Treatment:

Drug: Maridebart Cafraglutide

Placebo

Placebo Comparator group

Description:

Participants will receive placebo SC.

Treatment:

Drug: Placebo