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

Official title

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

Overview

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

• Drug Maridebart cafraglutide
  Maridebart cafraglutide will be administered as a SC injection.
• Drug Placebo
  Placebo will be administered as a SC injection.

Primary outcome measures

• Percent Change from Baseline in Liver Fat Content by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) at Week 52 [Time frame: Baseline and Week 52]
• Percent Change from Baseline in Body Weight at Week 52 [Time frame: Baseline and Week 52]

Secondary outcome measures (12)

• Number of Participants Achieving ≥ 30% Reduction from Baseline in Liver Fat Content (LFC) by MRI at Week 52 [Time frame: Baseline and Week 52]
• Percent Change from Baseline in Visceral Adipose Tissue (VAT) Volume by MRI at Week 52 [Time frame: Baseline and Week 52]
• Number of Participants Achieving < 5% LFC by MRI at Week 52 [Time frame: Week 52]
• Change from Baseline in LFC by MRI at Week 52 [Time frame: Baseline and Week 52]
• Percent Change from Baseline in LFC by MRI at Week 24 [Time frame: Baseline and Week 24]
• Change from Baseline in LFC by MRI at Week 24 [Time frame: Baseline and Week 24]
• Percent Change from Baseline in Thigh Muscle Volume by MRI at Week 24 and Week 52 [Time frame: Baseline, Week 24, and 52]
• Percent Change from Baseline in Thigh Muscle Fat Fraction by MRI at Week 24 and Week 52 [Time frame: Baseline, Week 24, and 52]
• Percent Change from Baseline in Thigh Intermuscular and Intramuscular Fat Volume by MRI at Week 24 and Week 52 [Time frame: Baseline, Week 24, and 52]
• Percent Change from Baseline in Abdominal Subcutaneous Adipose Tissue (ASAT) Volume by MRI at Week 52 [Time frame: Baseline and Week 52]
• Percent Change from Baseline in VAT Volume by MRI at Week 24 [Time frame: Baseline and Week 24]
• Percent Change from Baseline in ASAT Volume by MRI at Week 24 [Time frame: Baseline and Week 24]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 23 centers

• Arizona Clinical Trials — Chandler
• Medical Advancement Centers of Arizona — Phoenix
• Del Sol Research Management — Tucson
• San Fernando Valley Health Institute — Canoga Park
• Gastroenterology and Liver Institute — Escondido
• Inland Empire Liver Foundation — Rialto
• Apex Clinical Research — San Diego
• University of Florida College of Medicine-Jacksonville — Gainesville
• … and 15 more centers

Identifiers

NCT: NCT07441252 · 20230224

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗