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

A Phase 2a, Randomized, Active-Comparator-Controlled, Open-Label Study to Evaluate the Efficacy and Safety of Efinopegdutide (MK-6024) in Individuals With Nonalcoholic Fatty Liver Disease

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.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Efinopegdutide 20 mg/mL; Drug: Semaglutide 1.34 mg/mL

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0107)
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1119ACN
      • CIPREC-Laboratorio ( Site 0104)
    • Mar del Plata, Buenos Aires, Argentina, B7600FZO
      • Instituto de Investigaciones Clínicas Mar del Plata ( Site 0101)
  • Caba
    • Ciudad Autonoma de Buenos Aires, Caba, Argentina, C1425AGC
      • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada ( Site 0105)
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital-Gastroenterology & Hepatology ( Site 0204)
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre-Hepatology and Liver Transplant Medicine ( Site 0201)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Heritage Medical Research Clinic ( Site 0302)
• France
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital F-ENDOCRINOLOGY-DIABETOLOGY ( Site 0401)
  • Rhone
    • Pierre-Bénite, Rhone, France, 69310
      • centre hospitalier lyon sud-Endocrinologie, Diabète et Nutrition ( Site 0402)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus-Liver disease unit ( Site 0704)
  • Haifa, Israel, 3436212
    • Carmel Hospital-Liver Unit ( Site 0705)
  • Jerusalem, Israel, 9778419
    • Shaare Zedek Medical Center-Liver Unit ( Site 0703)
  • Petah-Tikva, Israel, 49100
    • Rabin Medical Center ( Site 0701)
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center-The Liver Diseases Center ( Site 0700)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center-Gastroenterology and Liver Disease ( Site 0702)
• Italy
  • Modena, Italy, 41125
    • Azienda Ospedaliero Universitaria ( Site 0803)
  • Verona, Italy, 37134
    • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Medicine ( Site 0804)
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Policlinico Umberto I ( Site 0801)
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 0805)
    • Rozzano, Lombardia, Italy, 20089
      • Humanitas-Medicina interna ed Epatologia ( Site 0800)
• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital-Gastroenterolgy/Hepatology ( Site 1303)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System ( Site 1305)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center-Gastroenterology/Internal Medicine ( Site 1302)
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital ( Site 1300)
  • Kyonggi-do
    • Bucheon, Kyonggi-do, Korea, Republic of, 14584
      • Soon Chun Hyang University Bucheon Hospital ( Site 1304)
• Mexico
  • Cuauhtémoc, Mexico, 06700
    • Centro de Investigación y Gastroenterología ( Site 0902)
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06700
      • Arké Estudios Clínicos S.A. de C.V.-Gastroenterology-Hepatology ( Site 0906)
    • Mexico City, Distrito Federal, Mexico, 14050
      • Medica Sur-Clinica de Enfermedades Digestivas y Obesidad ( Site 0908)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Avix Investigación Clinica, S.C. ( Site 0907)
  • Yucatan
    • Merida, Yucatan, Mexico, 97130
      • Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan (
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital-Liver Research Unit ( Site 1003)
  • Auckland, New Zealand, 2025
    • Middlemore Clinical Trials ( Site 1000)
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Christchurch Hospital-Gastroenterology Research ( Site 1002)
• Poland
  • Kujawsko-pomorskie
    • Torun, Kujawsko-pomorskie, Poland, 87-100
      • Nasz Lekarz Przychodnie Medyczne ( Site 1105)
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 01-868
      • Centrum Medyczne Pratia Warszawa ( Site 1107)
  • Slaskie
    • Katowice, Slaskie, Poland, 40-156
      • Clinical Medical Research ( Site 1101)
    • Mysowice, Slaskie, Poland, 41-400
      • ID Clinic ( Site 1100)
• Russian Federation
  • Moskovskaya Oblast
    • Dzerzhinskiy, Moskovskaya Oblast, Russian Federation, 140091
      • New Technologies of Medicine Clinic ( Site 1204)
  • Moskva
    • Moscow, Moskva, Russian Federation, 125008
      • Center targetnoy therapy ( Site 1203)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194358
      • Saint Petersburg City Polyclinic 117-endocrinology department ( Site 1201)
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 199226
      • Astarta Clinic ( Site 1202)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 1400)
  • Madrid, Spain, 28222
    • HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA-Gastroenterologia y Hepatologia ( Site 1402)
  • Sevilla, Spain, 41013
    • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Unidad de Ensayos Clínicos de Aparato Digestivo ( Site 1404)
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Hospital Universitario Virgen de la Victoria-UGC Endocrinologia y nutricion ( Site 1405)
  • La Coruna
    • Santiago de Compostela, La Coruna, Spain, 15706
      • CHUS - Hospital Clinico Universitario ( Site 1403)
• Taiwan
  • Tainan, Taiwan, 704
    • NATIONAL CHENG-KUNG UNI. HOSP.-Liver Research team of National Cheng Kung University Hospital ( Site
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 1501)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch-Division of hepatology, department of gastroenterology (
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Department of Hematology, Clinical Research Unit ( Site 1603)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi-internal diseases ( Site 1602)
  • Ankara, Turkey, 06560
    • Gazi Universitesi-gastroenterology ( Site 1605)
  • Istanbul, Turkey, 34093
    • Bezmialem Vakf Üniversitesi-Gastroenterology ( Site 1606)
  • Istanbul, Turkey, 34093
    • Istanbul University Capa Campus-Gastroenterology ( Site 1604)
  • Izmir
    • Balçova, Izmir, Turkey, 35330
      • Dokuz Eylül Üniversitesi-Endocrinology and Met. ( Site 1610)
• Ukraine
  • Kyiv, Ukraine, 02002
    • Adonis Plus-Outpatient department ( Site 1701)
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 310039
      • Ukrainian Research Institute of Therapy ( Site 1704)
    • Kharkiv, Kharkivska Oblast, Ukraine, 61039
      • L.T. Mala National Institute of Therapy of NAMS of Ukraine-Department of Aging Studies and Prevent
  • Poltavska Oblast
    • Poltava, Poltavska Oblast, Ukraine, 36011
      • Poltova Oblast Clinical Hospital IM.M.V.Sklifosovskoho ( Site 1710)
  • Zaporizka Oblast
    • Zaporizhia, Zaporizka Oblast, Ukraine, 69035
      • Communal Non-profit Enterprise "City Hospital #6" of Zaporizhzhia City Council-Therapy department (
• United States
  • California
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC ( Site 1939)
  • Florida
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty, Inc ( Site 1902)
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research, LLC ( Site 1950)
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare, LLC ( Site 1903)
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research, Inc ( Site 1930)
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute ( Site 1910)
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine-Advanced Liver Therapies ( Site 1960)
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute ( Site 1920)
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc. ( Site 1906)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efinopegdutide; 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.	Drug: Efinopegdutide 20 mg/mL; Subcutaneous injection in a dose-escalation administration of 2.4 mg, 5.0 mg, and 10.0 mg; Other Names: MK-6024; HM12525A; JNJ-64565111
Active Comparator: Semaglutide; 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.	Drug: Semaglutide 1.34 mg/mL; Subcutaneous injection in a dose-escalation administration of 0.25 mg, 0.5 mg, and 1.0 mg; Other Names: Ozempic®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline and up to ~24 Weeks
Percentage of Participants Who Experienced an Adverse Event (AE)	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.	Up to ~29 weeks
Percentage of Participants Who Discontinued Study Intervention Due to an AE	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.	Up to ~24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Absolute Reduction From Baseline in LFC Measured by MRI-PDFF (Evaluated by BICR) After 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.	Baseline and up to ~24 Weeks
Mean Percent Change From Baseline in Body Weight After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in Total Cholesterol After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in Triglycerides (TG) After 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.	Baseline and up to ~24 weeks
Mean Percent Change From Baseline in Apolipoprotein B (apoB) After 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.	Baseline and up to ~24 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Romero-Gomez M, Lawitz E, Shankar RR, Chaudhri E, Liu J, Lam RLH, Kaufman KD, Engel SS; MK-6024 P001 Study Group. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. J Hepatol. 2023 Oct;79(4):888-897. doi: 10.1016/j.jhep.2023.05.013. Epub 2023 Jun 22.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2021
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: June 28, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 6024-001; MK-6024-001 (Other Identifier: Merck); 2020-005136-30 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No