A Study of Efinopegdutide (MK-6024) in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) (MK-6024-001)
Condition: Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Efinopegdutide 20 mg/mL; Semaglutide 1.34 mg/mL
Intervention description: Subcutaneous injection in a dose-escalation administration of 2.4 mg, 5.0 mg, and 10.0 mg; Subcutaneous injection in a dose-escalation administration of 0.25 mg, 0.5 mg, and 1.0 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The principal goal of this study is to determine the efficacy of efinopegdutide in liver fat
      reduction in participants with NAFLD. The primary hypotheses are that efinopegdutide is
      superior to semaglutide, or that efinopegdutide is superior to semaglutide by at least 10%
      with respect to mean relative reduction from baseline in liver fat content (LFC) after 24
      weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  LFC ≥10% as assessed by MRI-PDFF at time of screening.

          -  Body Mass Index (BMI) ≥25 kg/m² and ≤50 kg/m² at time of screening.

          -  Stable weight (based on self-reporting) defined as ≤5% gain or loss of body weight for
             at least 3 months before screening visit.

          -  No history of Type 2 Diabetes Mellitus (T2DM) OR history of T2DM with an Glycated
             Hemoglobin (A1C) ≤8.5% at screening AND controlled by diet or a stable dose of
             metformin for the 3 months before screening.

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, is not a woman of childbearing potential (WOCBP), or is a WOCBP and
             agrees to follow contraceptive guidance during the study intervention period and for
             at least 5 weeks after the last dose of study intervention.

          -  Participants in Taiwan are eligible between the ages of 20 to 70 years of age
             (inclusive).

          -  Participants in South Korea are eligible between the ages of 19 to 70 years of age
             (inclusive).

        Exclusion Criteria:

          -  History of Type 1 Diabetes Mellitus (T1DM), diabetic ketoacidosis, or diabetes
             secondary to pancreatitis or pancreatectomy.

          -  Ongoing, inadequately controlled hypothyroidism or hyperthyroidism.

          -  Personal or family history of medullary thyroid carcinoma or multiple endocrine
             neoplasm type-2 syndrome.

          -  Recent event (within 6 months prior to screening) of congestive heart failure,
             unstable angina, myocardial infarction, arterial revascularization, stroke, or
             transient ischemic attack.

          -  History or evidence of chronic liver disease other than NAFLD or Non-Alcoholic
             SteatoHepatitis (NASH).

          -  Known history of cirrhosis.

          -  History of acute or chronic pancreatitis.

          -  History of a bariatric surgical procedure or a known clinically significant gastric
             emptying abnormality.

          -  History of malignancy ≤5 years prior to screening, except for skin cancer or cervical
             cancer.

          -  Clinically active hematologic disorder.

          -  Diagnosis of human immunodeficiency virus (HIV).

          -  Surgery requiring general anesthesia within 3 months before screening visit.

          -  History of organ transplantation, except for corneal transplant.

          -  Active diabetic proliferative retinopathy or a history of maculopathy.

          -  Untreated obstructive sleep apnea.

          -  History of treatment with any glucagon-like peptide-1 (GLP-1) receptor agonist within
             6 months before screening.

          -  History of treatment with thiazolidinediones (ie, pioglitazone, rosiglitazone) within
             6 months before screening.

          -  Previous use (within 3 months before screening) or current use of prescription
             weight-management medications or over-the-counter weight-loss medications or
             therapies.

          -  Treatment with systemic corticosteroid medication within 3 months before screening.

          -  Current treatment with anticoagulants (eg, warfarin, heparin).

          -  Inability to have an MRI-PDFF performed due to either severe claustrophobia, metallic
             implant that prevents MRI-PDFF examination, or any other contraindication to MRI-PDFF
             examination.

          -  Previous or current history of significant alcohol consumption (average of 7 standard
             drinks per week in females or 14 standard drinks per week in males) for a period of
             more than 3 consecutive months in the 24 months before screening.