A Study of Efinopegdutide (MK-6024) in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) (MK-6024-001)
- Conditions
- Nonalcoholic Fatty Liver DiseaseNonalcoholic Steatohepatitis
- Interventions
- 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
- 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).
- 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 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 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 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)
CIPREC-Laboratorio ( Site 0104)
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Carmel Hospital-Liver Unit ( Site 0705)
🇮🇱Haifa, Israel
Rabin Medical Center ( Site 0701)
🇮🇱Petah-Tikva, Israel
Sheba Medical Center-The Liver Diseases Center ( Site 0700)
🇮🇱Ramat Gan, Israel
Lucas Research, Inc ( Site 1930)
🇺🇸Morehead City, North Carolina, United States
Centro de Investigación y Gastroenterología ( Site 0902)
🇲🇽Cuauhtémoc, Mexico
Westmead Hospital-Gastroenterology & Hepatology ( Site 0204)
🇦🇺Westmead, New South Wales, Australia
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 0805)
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Medicine ( Site 0804)
🇮🇹Verona, Italy
Ankara University Department of Hematology, Clinical Research Unit ( Site 1603)
🇹🇷Ankara, Turkey
Bezmialem Vakf Üniversitesi-Gastroenterology ( Site 1606)
🇹🇷Istanbul, Turkey
Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital F-ENDOCRINOLOGY-DIABETOLOGY ( Site 0401)
🇫🇷Dijon, Cote-d Or, France
IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0107)
🇦🇷Buenos Aires, Argentina
Severance Hospital, Yonsei University Health System ( Site 1305)
🇰🇷Seoul, Korea, Republic of
Shaare Zedek Medical Center-Liver Unit ( Site 0703)
🇮🇱Jerusalem, Israel
Sourasky Medical Center-Gastroenterology and Liver Disease ( Site 0702)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero Universitaria ( Site 0803)
🇮🇹Modena, Italy
Gazi Universitesi-gastroenterology ( Site 1605)
🇹🇷Ankara, Turkey
Samsung Medical Center-Gastroenterology/Internal Medicine ( Site 1302)
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital ( Site 1300)
🇰🇷Seoul, Korea, Republic of
Dokuz Eylül Üniversitesi-Endocrinology and Met. ( Site 1610)
🇹🇷Balçova, Izmir, Turkey
Catalina Research Institute, LLC ( Site 1939)
🇺🇸Montclair, California, United States
Sensible Healthcare, LLC ( Site 1903)
🇺🇸Ocoee, Florida, United States
Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada ( Site 0105)
🇦🇷Ciudad Autonoma de Buenos Aires, Caba, Argentina
Humanitas-Medicina interna ed Epatologia ( Site 0800)
🇮🇹Rozzano, Lombardia, Italy
Inha University Hospital-Gastroenterolgy/Hepatology ( Site 1303)
🇰🇷Incheon, Korea, Republic of
Soon Chun Hyang University Bucheon Hospital ( Site 1304)
🇰🇷Bucheon, Kyonggi-do, Korea, Republic of
Centrum Medyczne Pratia Warszawa ( Site 1107)
🇵🇱Warsaw, Mazowieckie, Poland
Astarta Clinic ( Site 1202)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Istanbul University Capa Campus-Gastroenterology ( Site 1604)
🇹🇷Istanbul, Turkey
Communal Non-profit Enterprise "City Hospital #6" of Zaporizhzhia City Council-Therapy department (
🇺🇦Zaporizhia, Zaporizka Oblast, Ukraine
Hacettepe Universitesi-internal diseases ( Site 1602)
🇹🇷Ankara, Turkey
centre hospitalier lyon sud-Endocrinologie, Diabète et Nutrition ( Site 0402)
🇫🇷Pierre-Bénite, Rhone, France
Heritage Medical Research Clinic ( Site 0302)
🇨🇦Calgary, Alberta, Canada
Hospital Universitario Virgen de la Victoria-UGC Endocrinologia y nutricion ( Site 1405)
🇪🇸Malaga, Andalucia, Spain
CHUS - Hospital Clinico Universitario ( Site 1403)
🇪🇸Santiago de Compostela, La Coruna, Spain
Flinders Medical Centre-Hepatology and Liver Transplant Medicine ( Site 0201)
🇦🇺Bedford Park, South Australia, Australia
Auckland City Hospital-Liver Research Unit ( Site 1003)
🇳🇿Auckland, New Zealand
Middlemore Clinical Trials ( Site 1000)
🇳🇿Auckland, New Zealand
Christchurch Hospital-Gastroenterology Research ( Site 1002)
🇳🇿Christchurch, Canterbury, New Zealand
HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Unidad de Ensayos Clínicos de Aparato Digestivo ( Site 1404)
🇪🇸Sevilla, Spain
HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA-Gastroenterologia y Hepatologia ( Site 1402)
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 1400)
🇪🇸Barcelona, Spain
Avix Investigación Clinica, S.C. ( Site 0907)
🇲🇽Monterrey, Nuevo Leon, Mexico
Instituto de Investigaciones Clínicas Mar del Plata ( Site 0101)
🇦🇷Mar del Plata, Buenos Aires, Argentina
Medica Sur-Clinica de Enfermedades Digestivas y Obesidad ( Site 0908)
🇲🇽Mexico City, Distrito Federal, Mexico
Rambam Health Care Campus-Liver disease unit ( Site 0704)
🇮🇱Haifa, Israel
New Technologies of Medicine Clinic ( Site 1204)
🇷🇺Dzerzhinskiy, Moskovskaya Oblast, Russian Federation
Clinical Medical Research ( Site 1101)
🇵🇱Katowice, Slaskie, Poland
Adonis Plus-Outpatient department ( Site 1701)
🇺🇦Kyiv, Ukraine
National Taiwan University Hospital ( Site 1501)
🇨🇳Taipei, Taiwan
L.T. Mala National Institute of Therapy of NAMS of Ukraine-Department of Aging Studies and Prevent
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Policlinico Umberto I ( Site 0801)
🇮🇹Roma, Lazio, Italy
Arké Estudios Clínicos S.A. de C.V.-Gastroenterology-Hepatology ( Site 0906)
🇲🇽Mexico, Distrito Federal, Mexico
Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan (
🇲🇽Merida, Yucatan, Mexico
Nasz Lekarz Przychodnie Medyczne ( Site 1105)
🇵🇱Torun, Kujawsko-pomorskie, Poland
ID Clinic ( Site 1100)
🇵🇱Mysowice, Slaskie, Poland
Saint Petersburg City Polyclinic 117-endocrinology department ( Site 1201)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Ukrainian Research Institute of Therapy ( Site 1704)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Center targetnoy therapy ( Site 1203)
🇷🇺Moscow, Moskva, Russian Federation
Chang Gung Medical Foundation-Linkou Branch-Division of hepatology, department of gastroenterology (
🇨🇳Taoyuan, Taiwan
Poltova Oblast Clinical Hospital IM.M.V.Sklifosovskoho ( Site 1710)
🇺🇦Poltava, Poltavska Oblast, Ukraine
NATIONAL CHENG-KUNG UNI. HOSP.-Liver Research team of National Cheng Kung University Hospital ( Site
🇨🇳Tainan, Taiwan
Sweet Hope Research Specialty, Inc ( Site 1902)
🇺🇸Hialeah, Florida, United States
Floridian Clinical Research, LLC ( Site 1950)
🇺🇸Miami Lakes, Florida, United States
Baylor College of Medicine-Advanced Liver Therapies ( Site 1960)
🇺🇸Houston, Texas, United States
American Research Corporation at Texas Liver Institute ( Site 1920)
🇺🇸San Antonio, Texas, United States
Texas Clinical Research Institute ( Site 1910)
🇺🇸Arlington, Texas, United States
Clinical Trials of Texas, Inc. ( Site 1906)
🇺🇸San Antonio, Texas, United States