Overweight or Obesity and Elevated Liver Fat
Conditions
Keywords
Obesity, Overweight, Elevated liver fat, AMG 133, Maridebart cafraglutide
Brief summary
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.
Interventions
Maridebart cafraglutide will be administered as a SC injection.
DRUGPlacebo
Placebo will be administered as a SC injection.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Percent Change from Baseline in Body Weight at Week 52 | Baseline and Week 52 |
Secondary
| 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) |
Countries
United States
Contacts
CONTACTAmgen Call Center
STUDY_DIRECTORMD
Amgen
Outcome results
None listed