A Study of Efinopegdutide (MK-6024) in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) (MK-6024-001)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis

Treatments: Drug: Efinopegdutide 20 mg/mL; Drug: Semaglutide 1.34 mg/mL

Study type: Interventional

Funder types: Industry

Identifiers

NCT04944992

2020-005136-30 (EudraCT Number)

MK-6024-001 (Other Identifier)

6024-001

Details and patient eligibility

About

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.

Enrollment: 145 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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145 participants in 2 patient groups

Efinopegdutide

Experimental group

Description:

Efinopegdutide 20 mg/mL administered by injection once weekly for 24 weeks in a dose-escalation regimen: 2.4 mg from day 1 to week 3, 5.0 mg from week 4 to 7, and 10.0 mg from week 8 to 24.

Treatment:

Drug: Efinopegdutide 20 mg/mL

Semaglutide

Active Comparator group

Description:

Semaglutide 1.34 mg/mL administered by injection once weekly for 24 weeks in a dose-escalation regimen: 0.25 mg from day 1 to week 3, 0.5 mg from week 4 to 7, and 1.0 mg from week 8 to 24.

Treatment:

Drug: Semaglutide 1.34 mg/mL