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

Nonalcoholic Steatohepatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04944992
• Other study ID #: 6024-001
• Secondary ID: MK-6024-0012020-
• Status: Completed
• Phase: Phase 2
• Start date: August 4, 2021
• Est. completion date: October 19, 2022

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: October 19, 2022
• Est. primary completion date: October 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Efinopegdutide 20 mg/mL
Subcutaneous injection in a dose-escalation administration of 2.4 mg, 5.0 mg, and 10.0 mg
• Semaglutide 1.34 mg/mL
Subcutaneous injection in a dose-escalation administration of 0.25 mg, 0.5 mg, and 1.0 mg

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  France,  Israel,  Italy,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine, 

References & Publications (1)

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 liv — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information