A Study of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis (NASH) (MK-3655-001)

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04583423
• Other study ID #: 3655-001
• Secondary ID: MK-3655-001jRCT2
• Status: Terminated
• Phase: Phase 2
• Start date: November 11, 2020
• Est. completion date: April 13, 2023

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the effect of each dose of MK-3655 versus placebo on the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks. The primary hypothesis of the study is that at least 1 dose of MK-3655 is superior to placebo with respect to the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 183
• Est. completion date: April 13, 2023
• Est. primary completion date: April 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Has histological confirmation of NASH

• Is a male or female aged 18 years to 80 years (in Japan and Taiwan aged 20 to 80 years)

• Has a body mass index (BMI) =25 kg/m^2 and =50 kg/m^2 and stable weight for the past 3 months

• Has no history of Type 2 diabetes mellitus (T2DM) OR a history of T2DM controlled by diet or stable doses of antihyperglycemic agents (AHAs)

• Contraceptive use by male participants should be consistent with local regulations.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and she is not a woman of child-bearing potential (WOCBP) OR she is a WOCBP and uses a contraceptive method that is highly effective during the intervention period and for at least 16 weeks after the last dose of study intervention.

Exclusion Criteria

• Has presence of cirrhosis on liver biopsy

• Has Type 1 diabetes

• Has a history of malignancy, unless cancer free =5 years, or is under evaluation for active or suspected malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer

• Has a history of bariatric surgery =5 years before study participation

• Has undergone a major surgical procedure =3 months before study participation or has major surgery planned during the study

• Has a history or evidence of chronic liver disease other than NASH. Individuals with a history of Hepatitis B or C may be eligible for participation.

• Has significant systemic or major illnesses other than liver disease, including recent events (=6 months before study entry) of congestive heart failure, unstable coronary artery disease, arterial revascularization, pulmonary disease, renal failure, stroke, transient ischemic attack, or organ transplantation

Related Conditions & MeSH terms

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

Intervention

Drug:
• MK-3655
MK-3655 50, 100 or 300 dose for injection
• Placebo
Matching placebo to MK-3655

Locations

Country	Name	City	State
Argentina	Glenny Corp. S.A.-CLINICAL RESEARCH ( Site 0013)	Buenos Aires	Caba
Argentina	Hospital Aleman ( Site 0009)	Buenos Aires
Argentina	Hospital Británico de Buenos Aires ( Site 0002)	Buenos Aires	Caba
Argentina	Hospital Italiano de Buenos Aires-Hepatology ( Site 0014)	Ciudad de Buenos Aires	Caba
Argentina	Instituto de Investigaciones Clínicas Mar del Plata ( Site 0010)	Mar del Plata	Buenos Aires
Argentina	Hospital Universitario Austral ( Site 0003)	Pilar	Buenos Aires
Argentina	DIM Clínica Privada ( Site 0011)	Ramos Mejía	Buenos Aires
Argentina	Hospital Provincial del Centenario ( Site 0007)	Rosario	Santa Fe
Argentina	Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0008)	Santa Fe
Australia	Flinders Medical Centre ( Site 0107)	Bedford Park	South Australia
Australia	Royal Prince Alfred Hospital ( Site 0102)	Camperdown	New South Wales
Australia	St George Hospital ( Site 0104)	Kogarah	New South Wales
Canada	McGill University Health Centre ( Site 0400)	Montréal	Quebec
Canada	University Health Network - Toronto General Hospital ( Site 0401)	Toronto	Ontario
Canada	GIRI GI Research Institute - Vancouver ( Site 0404)	Vancouver	British Columbia
Chile	Hospital Regional de Concepcion ( Site 0505)	Concepcion	Biobio
Chile	Hospital San Juan de Dios de La Serena ( Site 0500)	La Serena	Coquimbo
Chile	Enroll SpA ( Site 0508)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 0501)	Santiago	Region M. De Santiago
Chile	Clinical Research Chile SpA ( Site 0506)	Valdivia	Los Rios
Chile	Centro de Investigaciones Clinicas Vina del Mar ( Site 0502)	Vina del Mar	Valparaiso
China	Beijing YouAn Hospital, Capital Medical University ( Site 0605)	Beijing	Beijing
China	The First People's Hospital of Foshan-Infection Department ( Site 0612)	Foshan	Guangdong
China	The Affiliated Hospital of Hangzhou Normal University ( Site 0600)	Hangzhou	Zhejiang
China	Xinhua Hospital Affiliated to Jiaotong University School of Medicine ( Site 0602)	Shanghai	Shanghai
China	Chongqing Three Gorges Central Hospital ( Site 0618)	Wanzhou District	Chongqing
China	General Hospital of Ningxia Medical University ( Site 0607)	Yinchuan City	Ningxia
Colombia	Fundacion Santa Fe de Bogota ( Site 0705)	Bogotá	Distrito Capital De Bogota
France	CHU Besançon ( Site 0806)	Besançon	Franche-Comte
France	Hôpital Beaujon ( Site 0804)	Clichy	Hauts-de-Seine
France	Hopital Henri Mondor ( Site 0808)	Creteil	Val-de-Marne
France	CHU Dijon Bourgogne - Hopital F. Mitterrand ( Site 0816)	Dijon	Bourgogne
France	Hôpital Claude Huriez ( Site 0811)	Lille	Nord
France	Centre Hospitalier et Universitaire Dupuytren ( Site 0810)	Limoges	Haute-Vienne
France	Hopital de la Croix-Rousse ( Site 0809)	Lyon	Auvergne
France	CHU de Nice Hopital de l Archet II ( Site 0800)	Nice	Alpes-Maritimes
France	A.P.H. Paris, Hopital Saint Antoine ( Site 0807)	Paris
France	Hopital de la Pitie Salpetriere ( Site 0813)	Paris
France	Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 0812)	Paris
France	hopital haut leveque chu de bordeaux-Service d'Hépato-gastroentérologie ( Site 0805)	Pessac	Aquitaine
France	C.H.U. Nancy Hopital de Brabois ( Site 0803)	Vandoeuvre les Nancy	Meurthe-et-Moselle
Germany	Charite Universitaetsmedizin Berlin ( Site 0443)	Berlin
Germany	Universitätsklinikum Frankfurt-Medizinische Klinik 1 ( Site 0445)	Frankfurt	Hessen
Germany	Universitaetsklinikum Freiburg ( Site 0446)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Leipzig ( Site 0447)	Leipzig	Sachsen
Germany	Johannes Gutenberg Universitat Mainz ( Site 0442)	Mainz	Rheinland-Pfalz
Greece	Hippokration University Hopsital-4th Department of Internal Medicine ( Site 3300)	Thessaloniki	Kentriki Makedonia
Hong Kong	Queen Mary Hospital ( Site 1003)	Hong Kong
Hong Kong	Prince of Wales Hospital ( Site 1001)	Shatin
Hong Kong	Prince of Wales Hospital ( Site 1002)	Shatin
Israel	Carmel Medical Center ( Site 1203)	Haifa
Israel	Rambam Medical Center ( Site 1201)	Haifa
Israel	Shaare Zedek Medical Center ( Site 1205)	Jerusalem
Israel	Rabin Medical Center ( Site 1204)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 1200)	Ramat Gan
Israel	Maccabi Health Services - Ramat Hasharon ( Site 1206)	Ramat Hasharon
Israel	Sourasky Medical Center ( Site 1202)	Tel Aviv
Italy	A O U Policlinico di Modena ( Site 1307)	Modena
Italy	Azienda Ospedaliera Policlinico Umberto I ( Site 1300)	Roma
Italy	IRCCS Istituto Clinico Humanitas di Rozzano ( Site 1303)	Rozzano	Lombardia
Italy	Azienda Ospedaliera Universitaria Integrata Verona ( Site 1301)	Verona
Japan	Fukui-ken Saiseikai Hospital ( Site 1410)	Fukui
Japan	Gifu Municipal Hospital ( Site 1408)	Gifu
Japan	Hiroshima University Hospital ( Site 1413)	Hiroshima
Japan	Kagoshima University Hospital ( Site 1418)	Kagoshima
Japan	Kanazawa University Hospital ( Site 1419)	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital ( Site 1407)	Kashihara	Nara
Japan	Shinyurigaoka General Hospital ( Site 1420)	Kawasaki	Kanagawa
Japan	Kagawa University Hospital ( Site 1414)	Kita-gun	Kagawa
Japan	University Hospital, Kyoto Prefectural University of Medicine ( Site 1405)	Kyoto
Japan	Aichi Medical University Hospital ( Site 1402)	Nagakute	Aichi
Japan	Ogaki Municipal Hospital ( Site 1409)	Ogaki	Gifu
Japan	Kawasaki Medical School General Medical Center ( Site 1412)	Okayama
Japan	Osaka Metropolitan University Hospital ( Site 1415)	Osaka
Japan	Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 1404)	Sapporo	Hokkaido
Japan	Saiseikai Suita Hospital ( Site 1403)	Suita	Osaka
Japan	Kagawa Prefectural Central Hospital-liver intemal medicine ( Site 1416)	Takamatsu	Kagawa
Japan	Toranomon Hospital ( Site 1401)	Tokyo
Japan	Ehime University Hospital ( Site 1417)	Toon	Ehime
Japan	Yokohama City University Hospital ( Site 1411)	Yokohama	Kanagawa
Korea, Republic of	Pusan National University Hospital-Internal Medicine ( Site 2010)	Busan	Pusan-Kwangyokshi
Korea, Republic of	Chungang University Hospital ( Site 2007)	Dongjak-gu	Seoul
Korea, Republic of	Inha University Hospital-Gastroenterolgy/Hepatology ( Site 2006)	Incheon
Korea, Republic of	Seoul National University Bundang Hospital-Internal Medicine ( Site 2005)	Seongnam	Kyonggi-do
Korea, Republic of	Hanyang University Seoul Hospital ( Site 2002)	Seoul
Korea, Republic of	Korea University Guro Hospital ( Site 2004)	Seoul
Korea, Republic of	Samsung Medical Center-Gastroenterology/Internal Medicine ( Site 2008)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2003)	Seoul
Korea, Republic of	Asan Medical Center ( Site 2001)	Songpagu	Seoul
Malaysia	Hospital Kuala Lumpur-Gastroenterology Department ( Site 2701)	Kuala Lumpur
Mexico	Centro de Investigacion Medico Biologica y Terapia Avanzada SC ( Site 1511)	Guadalajara	Jalisco
Mexico	Medical Care and Research S.A. de C.V. ( Site 1506)	Merida	Yucatan
Mexico	Centro de Investigacion y Gastroenterologia SC ( Site 1503)	Mexico City
Mexico	Medica Sur-Clinica de Enfermedades Digestivas y Obesidad ( Site 1515)	Mexico City	Distrito Federal
Mexico	Centro de Investigacion Medica de Occidente S.C. ( Site 1514)	Zapopan	Jalisco
New Zealand	Auckland Clinical Studies Limited ( Site 1600)	Auckland
New Zealand	Middlemore Clinical Trials ( Site 1601)	Auckland
New Zealand	Christchurch Hospital ( Site 1602)	Christchurch	Canterbury
Puerto Rico	Pan American Center for Oncology Trials ( Site 3102)	Rio Piedras
Puerto Rico	FDI Clinical Research ( Site 3101)	San Juan
Puerto Rico	Klinical Investigations Group ( Site 3100)	San Juan
Russian Federation	Center targetnoy therapy-Gastroenterology ( Site 1918)	Moscow	Moskva
Russian Federation	City Clinical Hospital named V.M.Buyanova ( Site 1922)	Moscow	Moskva
Russian Federation	Medical Rehabilitation Center ( Site 1904)	Moscow	Moskva
Russian Federation	Nephrology Clinic of Internal and Prof. Diseases n.a.E.M.Tareev ( Site 1906)	Moscow	Moskva
Russian Federation	Russian University of People Friendship ( Site 1907)	Moscow	Moskva
Russian Federation	LLC Astarta ( Site 1912)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Scientific research center ECO-security ( Site 1920)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Surgical Clinic "Parada" ( Site 1921)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SPb State Budgetary Institution Health Care City Policlinic 17 ( Site 1910)	St -Petersburg	Sankt-Peterburg
Spain	Hospital Clinic de Barcelona ( Site 2102)	Barcelona
Spain	Hospital Universitari Vall d Hebron ( Site 2101)	Barcelona
Spain	Hospital Universitario Puerta de Hierro-Majadahonda ( Site 2100)	Majadahonda	Madrid
Spain	Hospital Universitario Marqués de Valdecilla-Gastroenterology and Hepatology ( Site 2106)	Santander	Cantabria
Spain	Hospital Clinico Universitario de Santiago ( Site 2104)	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Virgen del Rocio ( Site 2105)	Sevila	Sevilla
Sweden	Karolinska Universitetssjukhuset Huddinge ( Site 2900)	Huddinge	Stockholms Lan
Sweden	Akademiska sjukhuset ( Site 2901)	Uppsala	Uppsala Lan
Taiwan	Chiayi Christian Hospital ( Site 2308)	Chiayi City	Chiayi
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 2302)	Kaohsiung
Taiwan	Taichung Veterans General Hospital ( Site 2306)	Taichung
Taiwan	Chung Shan Medical University Hospital ( Site 2307)	Taichung City	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 2304)	Tainan
Taiwan	National Taiwan University Hospital ( Site 2301)	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch ( Site 2305)	Taoyuan County	Taoyuan
Turkey	Ankara University Cebeci Research and Application Hospital ( Site 2406)	Ankara
Turkey	Gazi University Medical Faculty ( Site 2405)	Ankara
Turkey	Hacettepe Uni. Ic Hastaliklari Anabilim Dali, Nefroloji BD ( Site 2403)	Ankara
Turkey	Bezmialem Vakf Üniversitesi-Gastroenterology ( Site 2402)	Istanbul
Turkey	Istanbul Universitesi Tip Fakultesi Hastanesi ( Site 2401)	Istanbul
Turkey	Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 2400)	Istanbul
Turkey	Ege University Medical Faculty ( Site 2404)	Izmir
United States	Texas Clinical Research Institute ( Site 2619)	Arlington	Texas
United States	The National Diabetes & Obesity Research Institute ( Site 9017)	Biloxi	Mississippi
United States	Hope Clinical Research, Inc. ( Site 2601)	Canoga Park	California
United States	Premier Medical Group ( Site 9010)	Clarksville	Tennessee
United States	Peak Gastroenterology Associates ( Site 2645)	Colorado Springs	Colorado
United States	Top Medical Research, Inc ( Site 2673)	Cutler Bay	Florida
United States	The Liver Institute at Methodist Dallas Medical Center ( Site 2638)	Dallas	Texas
United States	Southeast Clinical Research Center ( Site 9003)	Dalton	Georgia
United States	Velocity Clinical Research, Syracuse ( Site 9016)	East Syracuse	New York
United States	DHR Health Institute for Research and Development ( Site 9006)	Edinburg	Texas
United States	South Texas Research Institute ( Site 9012)	Edinburg	Texas
United States	Hillmont G.I. ( Site 9019)	Flourtown	Pennsylvania
United States	Covenant Metabolic Specialists, LLC ( Site 9027)	Fort Myers	Florida
United States	North Florida South Georgia Veterans Health System ( Site 2613)	Gainesville	Florida
United States	Indago Research and Health Center Inc ( Site 2610)	Hialeah	Florida
United States	Sweet Hope Research Specialty Inc ( Site 2660)	Hialeah	Florida
United States	Baylor College of Medicine - Advanced Liver Therapies ( Site 2670)	Houston	Texas
United States	The Crofoot Research Center, Inc. ( Site 2611)	Houston	Texas
United States	Velocity Clinical Research, Huntington Park ( Site 9022)	Huntington Park	California
United States	The University of Iowa ( Site 2655)	Iowa City	Iowa
United States	Kansas City Research Institute ( Site 9018)	Kansas City	Missouri
United States	UCSD - Altman Clinical and Translational Research Institute -UC San Diego NAFLD Research Center ( Si	La Jolla	California
United States	Regional Gastroenterology Associates of Lancaster, LTD ( Site 9020)	Lancaster	Pennsylvania
United States	Excel Clinical Research, LLC ( Site 2603)	Las Vegas	Nevada
United States	Ruane Clinical Research Group, Inc ( Site 9014)	Los Angeles	California
United States	Velocity Clinical Research, Westlake ( Site 9013)	Los Angeles	California
United States	Legacy Clinical Solutions: Tandem Clinical Research, LLC ( Site 2650)	Marrero	Louisiana
United States	Genoma Research Group, Inc. ( Site 2669)	Miami	Florida
United States	Floridian Clinical Research, LLC ( Site 2656)	Miami Lakes	Florida
United States	Ocean Blue Medical Research Center Inc ( Site 2667)	Miami Springs	Florida
United States	Catalina Research Institute, LLC ( Site 2643)	Montclair	California
United States	NYU Langone Health, New York ( Site 2627)	New York	New York
United States	Arkansas Gastroenterology - North Little Rock ( Site 9015)	North Little Rock	Arkansas
United States	Sensible Healthcare Llc ( Site 2607)	Ocoee	Florida
United States	Synexus Research ( Site 2672)	Orlando	Florida
United States	Velocity Clinical Research, Panorama City ( Site 9001)	Panorama City	California
United States	California Liver Research Institute ( Site 9025)	Pasadena	California
United States	Virginia Commonwealth University Health System ( Site 2657)	Richmond	Virginia
United States	American Research Corporation at Texas Liver Institute ( Site 2634)	San Antonio	Texas
United States	Clinical Trials of Texas, LLC ( Site 2614)	San Antonio	Texas
United States	Quality Research ( Site 9024)	San Antonio	Texas
United States	Quest Clinical Research ( Site 9011)	San Francisco	California
United States	Velocity Clinical Research, Santa Ana ( Site 9002)	Santa Ana	California
United States	Adobe Clinical Research, LLC ( Site 2644)	Tucson	Arizona
United States	Arizona Liver Health ( Site 9026)	Tucson	Arizona
United States	Del Sol Research Management ( Site 2674)	Tucson	Arizona
United States	Impact Research Institute ( Site 2685)	Waco	Texas
United States	Regional Gastroenterology Associates of Lancaster, LTD ( Site 9004)	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  China,  Colombia,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  New Zealand,  Puerto Rico,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 52 Weeks	The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) was used to assess treatment response. The NASH CRN scoring scales were: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution was defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis.	Week 52
Primary	Percentage of Participants Who Experienced an Adverse Event (AE)	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to 64 weeks
Primary	Percentage of Participants Discontinuing Study Medication Due to an AE	An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.	Up to 52 weeks
Secondary	Mean Percent Relative Reduction From Baseline in Liver Fat Content (LFC) After 24 Weeks	LFC % was measured by Magnetic Resonance Imaging-Estimated Proton Density Fat Fraction (MRI-PDFF) and evaluated by BICR. MRI-PDFF is a highly accurate noninvasive measure of the proportion of fat content of a tissue.	Baseline and Week 24
Secondary	Percentage of Participants With =1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis Assessed With the NASH CRN Scoring System After 52 Weeks	Participants were evaluated with the NASH CRN scoring system with BICR with =1 stage improvement in fibrosis without worsening of steatohepatitis defined as no increase in the ballooning, inflammation, or steatosis scores.	Week 52
Secondary	Percentage of Participants With =2 Point Improvement in NAS With =1 Point Improvement in Inflammation or Ballooning Without Worsening of Fbrosis by Histology (Evaluated by BICR) After 52 Weeks	Participants with =2 point improvement in the NAS with =1 point improvement in inflammation or ballooning without worsening of fibrosis were assessed with the NASH CRN scoring system (evaluated by BICR). The NAS was calculated as the unweighted sum of the scores and ranges from 0-8 (highest activity).	Week 52

External Links

•   Merck Clinical Trials Information