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

Phase 2

Completed

Conditions: Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis

Interventions: Drug: Semaglutide 1.34 mg/mL
Drug: Efinopegdutide 20 mg/mL

Registration Number: NCT04944992

Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 145

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide	Semaglutide 1.34 mg/mL	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.
Efinopegdutide	Efinopegdutide 20 mg/mL	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Discontinued Study Intervention Due to an AE	Up to ~24 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to adverse event is presented.
Percentage of Participants Who Experienced an Adverse Event (AE)	Up to ~29 weeks	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an adverse event is presented.
Mean Relative Reduction From Baseline in Liver Fat Content (LFC) Measured by Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF), Evaluated by Blinded Independent Central Review (BICR) After 24 Weeks	Baseline and up to ~24 Weeks	LFC was measured with liver images taken by MRI-PDFF and analyzed by BICR. Relative Reduction from Baseline to Week 24 = (Baseline - Week 24) / Baseline x 100%. Mean relative reduction from baseline in liver fat content is presented.

Secondary Outcome Measures

Name	Time	Method
Mean Absolute Reduction From Baseline in LFC Measured by MRI-PDFF (Evaluated by BICR) After 24 Weeks	Baseline and up to ~24 Weeks	LFC was measured by liver images taken by MRI-PDFF and analyzed by BICR. The absolute reduction from baseline to Week 24 = Baseline - Week 24. The mean absolute reduction from baseline in LFC after 24 weeks of treatment is presented.
Mean Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in HDL-C. Mean percent change in HDL-C is presented.
Mean Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in LDL-C. The mean percent change in LDL-C is presented.
Mean Percent Change From Baseline in Total Cholesterol After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in total cholesterol. The mean percent change in total cholesterol is presented.
Mean Percent Change From Baseline in Triglycerides (TG) After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in triglycerides. The mean percent change in triglycerides is presented.
Mean Percent Change From Baseline in Body Weight After 24 Weeks	Baseline and up to ~24 weeks	Body weight in kilograms was measured using a standardized, digital scale. The mean percent change from baseline in body weight after 24 weeks is presented.
Mean Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in non-HDL-C. The mean percent change in non-HDL-C is presented.
Mean Percent Change From Baseline in Apolipoprotein B (apoB) After 24 Weeks	Baseline and up to ~24 weeks	Fasting blood samples were collected at baseline and after 24 weeks of treatment to assess mean percent change in apoB. The mean percent change in apoB is presented.

Trial Locations

Locations (69): Catalina Research Institute, LLC ( Site 1939)
🇺🇸
Montclair, California, United States
Sweet Hope Research Specialty, Inc ( Site 1902)
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Hialeah, Florida, United States
Floridian Clinical Research, LLC ( Site 1950)
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Miami Lakes, Florida, United States
Sensible Healthcare, LLC ( Site 1903)
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Ocoee, Florida, United States
Lucas Research, Inc ( Site 1930)
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Morehead City, North Carolina, United States
Texas Clinical Research Institute ( Site 1910)
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Arlington, Texas, United States
Baylor College of Medicine-Advanced Liver Therapies ( Site 1960)
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Houston, Texas, United States
American Research Corporation at Texas Liver Institute ( Site 1920)
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San Antonio, Texas, United States
Clinical Trials of Texas, Inc. ( Site 1906)
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San Antonio, Texas, United States
CIPREC-Laboratorio ( Site 0104)
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
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Catalina Research Institute, LLC ( Site 1939)
🇺🇸Montclair, California, United States