Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity

Phase 3RecruitingNCT07037433

Amgen12,800 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

12,800

Conditions

Atherosclerotic Cardiovascular Disease Overweight Obesity

Interventions

Maridebart CafraglutideDRUG

Maridebart cafraglutide will be administered SC.

PlaceboDRUG

Placebo will be administered SC.

Eligibility

Sex: ALLMin age: 45 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Locations (781)

Outcomes

Primary Outcomes

Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE])

Time frame: Up to approximately 35 months

Time to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, MI, Ischemic Stroke, Coronary Revascularization, or Heart Failure (HF) Event (5-point MACE)

Time frame: Up to approximately 35 months

Secondary Outcomes

Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or HF Event

Time frame: Up to approximately 35 months

Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke or Coronary Revascularization

Time frame: Up to approximately 35 months

Time to First MI

Time frame: Up to approximately 35 months

Time to First Ischemic Stroke

Time frame: Up to approximately 35 months

Time to CV Death

Time frame: Up to approximately 35 months

Time to All-cause Death

Time frame: Up to approximately 35 months

Time to First Coronary Revascularization

Time frame: Up to approximately 35 months

Time to First HF Event

Time frame: Up to approximately 35 months

Central Contacts

Amgen Call Center

CONTACT

866-572-6436 medinfo@amgen.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Alliance For Multispecialty Research - Daphne

Daphne, Alabama, United States

RECRUITING

Eastern Shore Research Institute

Fairhope, Alabama, United States

RECRUITING

Heart Center Research LLC

Huntsville, Alabama, United States

RECRUITING

Mobile Heart Specialists PC

Mobile, Alabama, United States

RECRUITING

Syed Research Consultants LLC

Sheffield, Alabama, United States

RECRUITING

Synexus Clinical Research US, Inc.

Phoenix, Arizona, United States

RECRUITING

Medical Advancement Centers of Arizona

Phoenix, Arizona, United States

RECRUITING

Valley Clinical Trials, LLC dba Flourish Research

Covina, California, United States

RECRUITING

Velocity Clinical Research- Huntington Park

Huntington Park, California, United States

RECRUITING

Velocity Clinical Research- Los Angeles

La Mesa, California, United States

COMPLETED

...and 771 more locations

Time to First HF Event or CV Death

Time frame: Up to approximately 35 months

Time to First Unstable Angina Requiring Hospitalization

Time frame: Up to approximately 35 months

Time to First Occurrence of MI or CV Death

Time frame: Up to approximately 35 months

Time to First Occurrence of MI, Ischemic Stroke or All-cause Death

Time frame: Up to approximately 35 months

Total Major Ischemic Events (Time to First and Recurrent MI or Ischemic Stroke)

Time frame: Up to approximately 35 months

Total All-cause Hospitalizations (Time to First and Recurrent Event)

Time frame: Up to approximately 35 months

Time to Onset of Type 2 Diabetes Mellitus (T2DM) in Participants with Prediabetes at Baseline

Time frame: Up to approximately 35 months

Time to Onset of T2DM in Participants without T2DM at Baseline

Time frame: Up to approximately 35 months

Change from Baseline in Systolic Blood Pressure (SBP) at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Diastolic Blood Pressure (DBP) at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Body Mass Index (BMI) at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Waist Circumference at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Urine Albumin-to-creatinine Ratio (uACR) at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Hemoglobin A1c (HbA1c) at Week 72

Time frame: Baseline and Week 72

Change from Baseline in Fasting Plasma Glucose at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in Body Weight at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in Total Cholesterol at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 72

Time frame: Baseline and Week 72

Percent Change from Baseline in Triglycerides (TG) at Week 72

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 6.5% (48 mmol/mol) in Participants with T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 6.0% (42 mmol/mol) in Participants with T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants with T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 6.5% (48 mmol/mol) in Participants Without T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 6.0% (42 mmol/mol) in Participants Without T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants Without T2DM at Baseline

Time frame: Baseline and Week 72

Number of Participants at Week 72 with HbA1c < 5.7% (39 mmol/mol) in Participants with HbA1c ≥ 5.7% and < 6.5% at Baseline

Time frame: Baseline and Week 72

Change from Baseline in Short Form 36 Health Survey Acute Version 2 (SF-36 v2) Physical Function Domain Score at Week 48

Time frame: Baseline and Week 48

Time to First Event of a Composite Nephropathy Endpoint

Composite endpoint consists of onset of persistent macroalbuminuria, persistent ≥ 40% reduction in estimated glomerular filtration rate (eGFR), onset of persistent eGFR \< 15 mL/min/1.73 m\^2, initiation of chronic renal replacement therapy (dialysis or transplantation), CV or renal death.

Time frame: Up to approximately 35 months

Change in eGFR (total slope) for the period from baseline to the final follow up visit

Time frame: Baseline up to approximately 35 months

Change in eGFR (chronic slope) for the period from 4 months to the final follow-up visit

Time frame: From 4 months up to approximately 35 months

Time to First Occurrence of a Major Adverse Limb Event (MALE) Defined as Acute Limb Ischemia, Urgent Peripheral Revascularization, Major Amputation Due to a Vascular Etiology or Chronic Limb-threatening Ischemia Requiring Revascularization

Time frame: Up to approximately 35 months

Total Arterial (Coronary, Cerebrovascular, and Peripheral) Revascularization Procedures (Time to First and Recurrent Event)

Time frame: Up to approximately 35 months

Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, MALE, or Arterial Revascularization

Time frame: Up to approximately 35 months

Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or Acute Limb Ischemia

Time frame: Up to approximately 35 months

Time to First Occurrence of a Composite Endpoint Consisting of CV Death, MI, Ischemic Stroke, Acute Limb Ischemia, or Urgent Arterial Revascularization Procedure (Coronary, Cerebrovascular or Peripheral)

Time frame: Up to approximately 35 months

Number of Participants with Treatment-emergent Adverse Events

Time frame: Up to approximately 35 months

Number of Participants with Serious Adverse Events

Time frame: Up to approximately 35 months

Plasma Concentration of Maridebart Cafraglutide at Week 72

Time frame: Week 72