A Trial to Evaluate Efficacy and Safety of Maridebart Cafraglutide in Adults Living With Elevated Liver Fat and Obesity or Overweight

Phase 2b Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety and Tolerability of Maridebart Cafraglutide in Adult Participants Living With Elevated Liver Fat and Obesity or Overweight

The main objective of this trial will be to determine whether maridebart cafraglutide is superior to placebo on reduction in liver fat content and body weight in participants living with obesity or overweight and elevated liver fat content, when administered in conjunction with reduced-calorie diet and increased physical activity.

Study Overview

• Status: Recruiting
• Conditions: Overweight or Obesity and Elevated Liver Fat
• Intervention / Treatment: Drug: Placebo; Drug: Maridebart cafraglutide

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Arizona Clinical Trials
    • Phoenix, Arizona, United States, 85044
      • Recruiting
      • Medical Advancement Centers of Arizona
    • Tucson, Arizona, United States, 85715
      • Recruiting
      • Del Sol Research Management
  • California
    • Escondido, California, United States, 92025
      • Recruiting
      • Gastroenterology and Liver Institute
    • Rialto, California, United States, 92377
      • Recruiting
      • Inland Empire Liver Foundation
    • San Diego, California, United States, 92120
      • Recruiting
      • Apex Clinical Research
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida College of Medicine-Jacksonville
    • Hialeah, Florida, United States, 33012
      • Recruiting
      • Indago Research and Health Center
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Floridian Clinical Research LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Recruiting
      • Gastrointestinal Specialists- Louisiana Research Center- Highland
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Recruiting
      • Woodholme Gastroenterology Associates - Glen Burnie
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Recruiting
      • Alliance for Multispecialty Research - Kansas City
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Recruiting
      • Excel Clinical Research
  • Texas
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Bellaire Clinical Research
    • Bellaire, Texas, United States, 77401
      • Recruiting
      • Juno Research LLC
    • Corpus Christi, Texas, United States, 78404
      • Recruiting
      • Pinnacle Clinical Research - Corpus Christi
    • Edinburg, Texas, United States, 78539
      • Recruiting
      • South Texas Research Institute
    • Houston, Texas, United States, 77079
      • Recruiting
      • Houston Research Institute
    • Pasadena, Texas, United States, 77505
      • Recruiting
      • Houston Research Institute - Pasadena
    • Pharr, Texas, United States, 78557
      • Recruiting
      • McAllen Research
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • American Research Corporation at the Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Body Mass index (BMI) ≥ 27 kg/m^2 to ≤ 40 kg/m^2 at screening.
• For participants with type 2 diabetes mellitus (T2DM) at screening:
• HbA1c ≤ 9.5% (80 mmol/mol) at screening.
• Treated with diet and exercise alone and/or a stable treatment with metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, or combination.
• Liver Controlled Attenuation Parameter (CAPTM) ≥ 300 dB/meter via FibroScan® assessment.
• Liver fat content ≥ 10% by MRI as determined by the central imaging vendor at screening.
• MRI assessment should only be performed after all other eligibility has been confirmed whenever possible.
• History of at least 1 self-reported unsuccessful attempt at weight loss by diet and exercise.

Exclusion Criteria:

• Recent or planned surgical/device-based obesity treatment (<1 year).
• History of malignancy within the past 5 years (exceptions apply).
• Type 1 diabetes or non-type 2 diabetes mellitus (T2DM); unstable/severe hypoglycemia.
• Advanced diabetic retinopathy or macular edema.
• History of pancreatitis (acute <180 days or chronic).
• History of medullary thyroid carcinoma (MTC) or MEN-2
• Major cardiovascular event within 60 days (e.g., myocardial infarction [MI], stroke, coronary artery bypass graft [CABG]).
• New York Heart Association (NYHA) Class IV heart failure.
• Unstable psychiatric disorders within 2 years.
• Significant liver disease other than metabolic dysfunction-associated steatotic liver disease (MASLD) (e.g., hepatitis, cirrhosis, hepatic decompensation).
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 or on dialysis.
• Patient Health Questionnaire-9 (PHQ-9) ≥ 15, or suicidal ideation/behavior (Columbia-Suicide Severity Rating Scale [C-SSRS]).
• Inability to undergo MRI scan (e.g., due to metal implant, claustrophobia, or body size limitations).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maridebart Cafraglutide; Participants will receive maridebart cafraglutide as a subcutaneous (SC) injection every 4 weeks (Q4W) for 52 weeks.	Drug: Maridebart cafraglutide; Maridebart cafraglutide will be administered as a SC injection.; Other Names: AMG 133
Placebo Comparator: Placebo; Participants will receive placebo as a SC injection Q4W for 52 weeks.	Drug: Placebo; Placebo will be administered as a SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Body Weight at Week 52	Baseline and Week 52
Percent Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) at Week 52	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Achieving ≥ 30% Reduction from Baseline in Liver Fat Content (LFC) by MRI at Week 52	Baseline and Week 52
Percent Change from Baseline in Visceral Adipose Tissue (VAT) Volume by MRI at Week 52	Baseline and Week 52
Number of Participants Achieving < 5% LFC by MRI at Week 52	Week 52
Change from Baseline in LFC by MRI at Week 52	Baseline and Week 52
Percent Change from Baseline in LFC by MRI at Week 24	Baseline and Week 24
Change from Baseline in LFC by MRI at Week 24	Baseline and Week 24
Percent Change from Baseline in Thigh Muscle Volume by MRI at Week 24 and Week 52	Baseline, Week 24, and 52
Percent Change from Baseline in Thigh Muscle Fat Fraction by MRI at Week 24 and Week 52	Baseline, Week 24, and 52
Percent Change from Baseline in Thigh Intermuscular and Intramuscular Fat Volume by MRI at Week 24 and Week 52	Baseline, Week 24, and 52
Percent Change from Baseline in Abdominal Subcutaneous Adipose Tissue (ASAT) Volume by MRI at Week 52	Baseline and Week 52
Percent Change from Baseline in VAT Volume by MRI at Week 24	Baseline and Week 24
Percent Change from Baseline in ASAT Volume by MRI at Week 24	Baseline and Week 24
Change from Baseline in Waist Circumference at Week 52	Baseline and Week 52
Change from Baseline in Waist-to-height Ratio at Week 52	Baseline and Week 52
Change from Baseline in Aspartate Aminotransferase (AST) at Week 52	Baseline and Week 52
Change from Baseline in Alanine Aminotransferase (ALT) at Week 52	Baseline and Week 52
Change from Baseline in Gamma Glutamyl Transferase (GGT) at Week 52	Baseline and Week 52
Change from Baseline in Hemoglobin A1c (HbA1c) at Week 52	Baseline and Week 52
Change from Baseline in Fasting Glucose at Week 52	Baseline and Week 52
Percent Change from Baseline in Fasting Insulin at Week 52	Baseline and Week 52
Plasma Concentration of Maridebart Cafraglutide at Week 52	Week 52
Number of Participants Experiencing Treatment-emergent adverse events (TEAEs)	From first dose to end of trial (up to approximately 65 weeks)
Number of Participants Experiencing Serious AEs (SAEs)	From screening to end of trial (up to approximately 69 weeks)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2026
• Primary Completion (Estimated): September 29, 2027
• Study Completion (Estimated): December 22, 2027

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Overweight; AMG 133; Maridebart cafraglutide; Elevated liver fat
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: 20230224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this trial will be considered beginning 18 months after the trial has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this trial.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen trial/trials in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No