Clinical trial NCT04944992: A Study of Efinopegdutide (MK-6024) in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) (MK-6024-001)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: Baseline and up to ~24 Weeks
measure: Percentage of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to ~29 weeks
measure: Percentage of Participants Who Discontinued Study Intervention Due to an AE
timeFrame: Up to ~24 weeks
Secondary outcomes:
measure: Mean Absolute Reduction From Baseline in LFC Measured by MRI-PDFF (Evaluated by BICR) After 24 Weeks
timeFrame: Baseline and up to ~24 Weeks
measure: Mean Percent Change From Baseline in Body Weight After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in Total Cholesterol After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in Triglycerides (TG) After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
measure: Mean Percent Change From Baseline in Apolipoprotein B (apoB) After 24 Weeks
timeFrame: Baseline and up to ~24 weeks
Other outcomes:
Locations:
city: Montclair
country: United States
facility: Catalina Research Institute, LLC ( Site 1939)
state: California
city: Hialeah
country: United States
facility: Sweet Hope Research Specialty, Inc ( Site 1902)
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research, LLC ( Site 1950)
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare, LLC ( Site 1903)
state: Florida
city: Morehead City
country: United States
facility: Lucas Research, Inc ( Site 1930)
state: North Carolina
city: Arlington
country: United States
facility: Texas Clinical Research Institute ( Site 1910)
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine-Advanced Liver Therapies ( Site 1960)
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute ( Site 1920)
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc. ( Site 1906)
state: Texas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CIPREC-Laboratorio ( Site 0104)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata ( Site 0101)
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada ( Site 0105)
state: Caba
city: Buenos Aires
country: Argentina
facility: IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0107)
city: Westmead
country: Australia
facility: Westmead Hospital-Gastroenterology & Hepatology ( Site 0204)
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre-Hepatology and Liver Transplant Medicine ( Site 0201)
state: South Australia
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic ( Site 0302)
state: Alberta
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital F-ENDOCRINOLOGY-DIABETOLOGY ( Site 0401)
state: Cote-d Or
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud-Endocrinologie, Diabète et Nutrition ( Site 0402)
state: Rhone
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Liver disease unit ( Site 0704)
city: Haifa
country: Israel
facility: Carmel Hospital-Liver Unit ( Site 0705)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center-Liver Unit ( Site 0703)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center ( Site 0701)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-The Liver Diseases Center ( Site 0700)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center-Gastroenterology and Liver Disease ( Site 0702)
city: Roma
country: Italy
facility: Policlinico Umberto I ( Site 0801)
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico ( Site 0805)
state: Lombardia
city: Rozzano
country: Italy
facility: Humanitas-Medicina interna ed Epatologia ( Site 0800)
state: Lombardia
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria ( Site 0803)
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Medicine ( Site 0804)
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Bucheon Hospital ( Site 1304)
state: Kyonggi-do
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital-Gastroenterolgy/Hepatology ( Site 1303)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System ( Site 1305)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Gastroenterology/Internal Medicine ( Site 1302)
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital ( Site 1300)
city: Mexico City
country: Mexico
facility: Medica Sur-Clinica de Enfermedades Digestivas y Obesidad ( Site 0908)
state: Distrito Federal
city: Mexico
country: Mexico
facility: Arké Estudios Clínicos S.A. de C.V.-Gastroenterology-Hepatology ( Site 0906)
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Avix Investigación Clinica, S.C. ( Site 0907)
state: Nuevo Leon
city: Merida
country: Mexico
facility: Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en Yucatan (
state: Yucatan
city: Cuauhtémoc
country: Mexico
facility: Centro de Investigación y Gastroenterología ( Site 0902)
city: Christchurch
country: New Zealand
facility: Christchurch Hospital-Gastroenterology Research ( Site 1002)
state: Canterbury
city: Auckland
country: New Zealand
facility: Auckland City Hospital-Liver Research Unit ( Site 1003)
city: Auckland
country: New Zealand
facility: Middlemore Clinical Trials ( Site 1000)
city: Torun
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne ( Site 1105)
state: Kujawsko-pomorskie
city: Warsaw
country: Poland
facility: Centrum Medyczne Pratia Warszawa ( Site 1107)
state: Mazowieckie
city: Katowice
country: Poland
facility: Clinical Medical Research ( Site 1101)
state: Slaskie
city: Mysowice
country: Poland
facility: ID Clinic ( Site 1100)
state: Slaskie
city: Dzerzhinskiy
country: Russian Federation
facility: New Technologies of Medicine Clinic ( Site 1204)
state: Moskovskaya Oblast
city: Moscow
country: Russian Federation
facility: Center targetnoy therapy ( Site 1203)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg City Polyclinic 117-endocrinology department ( Site 1201)
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: Astarta Clinic ( Site 1202)
state: Sankt-Peterburg
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria-UGC Endocrinologia y nutricion ( Site 1405)
state: Andalucia
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario ( Site 1403)
state: La Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Liver Unit - Department of Internal Medicine ( Site 1400)
city: Madrid
country: Spain
facility: HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA-Gastroenterologia y Hepatologia ( Site 1402)
city: Sevilla
country: Spain
facility: HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Unidad de Ensayos Clínicos de Aparato Digestivo ( Site 1404)
city: Tainan
country: Taiwan
facility: NATIONAL CHENG-KUNG UNI. HOSP.-Liver Research team of National Cheng Kung University Hospital ( Site
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 1501)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch-Division of hepatology, department of gastroenterology (
city: Balçova
country: Turkey
facility: Dokuz Eylül Üniversitesi-Endocrinology and Met. ( Site 1610)
state: Izmir
city: Ankara
country: Turkey
facility: Ankara University Department of Hematology, Clinical Research Unit ( Site 1603)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi-internal diseases ( Site 1602)
city: Ankara
country: Turkey
facility: Gazi Universitesi-gastroenterology ( Site 1605)
city: Istanbul
country: Turkey
facility: Bezmialem Vakf Üniversitesi-Gastroenterology ( Site 1606)
city: Istanbul
country: Turkey
facility: Istanbul University Capa Campus-Gastroenterology ( Site 1604)
city: Kharkiv
country: Ukraine
facility: Ukrainian Research Institute of Therapy ( Site 1704)
state: Kharkivska Oblast
city: Kharkiv
country: Ukraine
facility: L.T. Mala National Institute of Therapy of NAMS of Ukraine-Department of Aging Studies and Prevent
state: Kharkivska Oblast
city: Poltava
country: Ukraine
facility: Poltova Oblast Clinical Hospital IM.M.V.Sklifosovskoho ( Site 1710)
state: Poltavska Oblast
city: Zaporizhia
country: Ukraine
facility: Communal Non-profit Enterprise "City Hospital #6" of Zaporizhzhia City Council-Therapy department (
state: Zaporizka Oblast
city: Kyiv
country: Ukraine
facility: Adonis Plus-Outpatient department ( Site 1701)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.