Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH)

Non-alcoholic Steatohepatitis Clinical Trial

— ESSENCE  

Official title:

The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04822181
• Other study ID #: NN9931-4553
• Secondary ID: U1111-1244-36782
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2021
• Est. completion date: April 25, 2029

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries.

Participants will either get semaglutide or a dummy medicine - which treatment participants get is decided by chance.

Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week.

The study will last for about 5 years. Participants will have up to 21 clinic visits and 9 phone calls with the clinical staff during the study. Some of the clinic visits may be spread over more than one day.

Participants with other chronic liver diseases cannot take part in this study. Women cannot take part in the study if they are pregnant, breast-feeding or plan to become pregnant during the study period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: April 25, 2029
• Est. primary completion date: April 25, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age above or equal to 18 years at the time of signing informed consent.

• Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to the screening visit (V1).

• Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy.

• A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 4 with a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.

Exclusion Criteria:

• Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD)

• Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).

• Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.

• Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).

• Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose from time of biopsy until screening.

• Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening (V2A).

• Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Semaglutide
Semaglutide administrated subcutaneously (under the skin) once weekly there will be a period of dose escalation before reaching the target dose.
• Placebo
Placebo administrated subcutaneously (under the skin) once weekly.

Locations

Country	Name	City	State
Argentina	DIM Clinica Privada	Buenos Aires
Argentina	Centro Médico Viamonte SRL	Caba
Argentina	Centro Médico Viamonte SRL	Caba
Argentina	Glenny Corp. S.A	Caba
Argentina	Hospital Italiano Departamento Hepatologia	Caba
Argentina	Centro de Investigaciones Metabólicas	Capital Federal
Argentina	Hospital Britanico de Buenos Aires	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hospital El Cruce	Florencio Varela, Buenos Aires
Argentina	Hospital del Centenario	Rosario, Santa Fe
Australia	Royal Adelaide Hospital - Hepatology- 5E291	Adelaide	South Australia
Australia	A.W. Morrow Gastroenterology and Liver Centre	Camperdown	New South Wales
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	St Vincent's Hospital (Melbourne)	Fitzroy	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Fiona Stanley Hospital - Hepatology	Murdoch	Western Australia
Australia	Sir Charles Gairdner Hospital_Nedlands	Nedlands	Western Australia
Australia	Griffith University Clinical Trial Unit	Southport	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Klin.Abt. f. Gastroenterologie u. Hepatologie	Graz
Austria	Fließer-Görzer [Ordination]	Saint Stefan
Austria	LKH Salzburg Universitätsklinikum	Salzburg
Austria	Klinikum Wels-Grieskirchen	Wels
Austria	Klinik Landstraße	Wien
Belgium	Cliniques Universitaires Saint-Luc - Serv. Hépato-gastroentérology	Bruxelles
Belgium	CUB Hôpital Erasme_Brussels_0	Bruxelles
Belgium	UZA	Edegem
Belgium	Ziekenhuis Oost-Limburg AV - Gastro	Genk
Belgium	AZ Maria Middelares - Gent - Gastro-Enterology	Gent
Belgium	UZ Gent - Department Gastro-enterology	Gent
Brazil	Fundação Pio XII	Barretos	São Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina de Botucatu	Botucatu	Sao Paulo
Brazil	Hospital das Clínicas da Universidade Federal de Goiás	Goiânia	Goias
Brazil	Hospital de Clínicas de Porto Alegre_Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro
Brazil	Fundação Bahiana de Infectologia	Salvador	Bahia
Brazil	CIP Centro Integrado de Pesquisas do Hospital de Base	São José do Rio Preto	Sao Paulo
Brazil	Assoc. Paulista para o Desenvolvimento da Medicina - UNIFESP	São Paulo	Sao Paulo
Brazil	Departamento de Gastroenterologia - HCFMUSP	São Paulo	Sao Paulo
Brazil	Rocco e Nazato Servicos Medicos LTDA	São Paulo
Bulgaria	"MHAT - UniHospital" OOD	Panagyurishte
Bulgaria	MHAT "Med Line Clinic"	Plovdiv
Bulgaria	"Acibadem City Clinic UMHAT Tokuda"	Sofia
Bulgaria	"DCC XX - Sofia" EOOD	Sofia
Bulgaria	"Diagnostic - Consulting Center Aleksandrovska" EOOD	Sofia
Bulgaria	"Medical Center Vertebra" Ltd.	Sofia
Bulgaria	"UMHAT "Sveta Anna" Sofia" AD	Sofia
Bulgaria	"UMHAT "Tsaritsa Yoanna-ISUL"" EAD, Gastroenterology clinic	Sofia
Bulgaria	"UMHAT "Tsaritsa Yoanna-ISUL"" EAD, Gastroenterology clinic	Sofia
Bulgaria	Acibadem City Clinic UMHAT Mladost	Sofia
Bulgaria	Medical Center Synexus Sofia	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", Clinic of Gastroenterology	Sofia
Bulgaria	UMHAT "Sveta Marina"	Varna
Canada	LMC ClinRsrh Inc.Brampton	Brampton	Ontario
Canada	University of Calgary Liver Unit-(HMRC)	Calgary	Alberta
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Nova Scotia Hlth Halifax	Halifax	Nova Scotia
Canada	London Hlth Sci Ctr- Univ Camp	London	Ontario
Canada	Clinique Medicine Urbaine du Quartier Latin, Inc.	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Hospital Fleurimont / CIUSS	Sherbrooke	Quebec
Canada	Ctr de Med Metab de Lanaudiere	Terrebonne	Quebec
Canada	Centricity Research LMC	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Canada	TDDA Specialty Research	Vaughan	Ontario
China	Beijing Ditan Hospital Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tsinghua Changgung Hospital-Hepatology	Beijing	Beijing
China	Beijing You'an Hospital, Capital Medical University	Beijing	Beijing
China	Peking University People's Hospital(White Pagoda Temple Area	Beijing	Beijing
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Changzhou No.2 People's Hospital	Changzhou	Jiangsu
China	West China Hospital, Sichuan University	Chengdu
China	Three Gorges Hospital Affiliated to Chongqing University	Chongqing	Chongqing
China	Foshan First People's Hospital	Foshan	Guangdong
China	Guangzhou Eighth People's Hospital	Guangzhou
China	Guangzhou First people's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital, Southern Medical University-1	Guangzhou	Guangdong
China	The 3rd Affiliated Hosp of Sun Yat-sen University,Infectious	Guangzhou	Guangdong
China	The First Affiliated Hospital , Sun Yat-sen University	Guangzhou
China	Zhejiang Hospital	Hangzhou
China	Jinan Central Hospital	Ji'nan	Shandong
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	Qingdao Municipal Hospital (Group)	Qingdao	Shandong
China	Renji Hospital Affiliated to Shanghai Jiaotong University	Shanghai	Shanghai
China	Ruijin Hospital Affiliate to The Shanghai Jiaotong Universit	Shanghai	Shanghai
China	Shanghai Ninth People's Hospital	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The Third People's Hospital of Shenzhen	Shenzhen
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Second People's Hospital	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin
China	The First Hospital Affiliated to Wenzhou Medical College	Wenzhou	Zhejiang
China	THE Affiliated Hospital of Xuzhou Medical University(East)	Xuzhou	Jiangsu
China	General Hosp of Ningxia Medical University,Infectious Depart	Yinchuan	Ningxia
China	The Third People's Hospital of Zhenjiang	Zhenjiang	Jiangsu
Croatia	Klinicki bolnicki centar Osijek	Osijek
Croatia	KBC Rijeka, Zavod za gastroenterologiju	Rijeka
Croatia	KBC Split/ Firule/ Gastroenterologija	Split
Croatia	KB Dubrava, Zavod za gastroenterologiju	Zagreb
Croatia	Klinicki bolnicki centar Zagreb, Zavod za gastroenterologiju	Zagreb
Czechia	Krajská nemocice Liberec, a.s	Liberec
Czechia	Krajská nemocice Liberec, a.s	Liberec
Czechia	Fakultni nemocnice Plzen - Lochotin	Plzen
Czechia	Researchsite s.r.o.	Plzen
Czechia	Vseobecna Fakultni nemocnice v Praze	Prague 2
Czechia	Vseobecna Fakultni nemocnice v Praze	Prague 2
Denmark	Aarhus Universitetshospital Skejby Mave-Tarm	Aarhus N
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Abdominal Center K, Research Unit	København NV
Denmark	Odense University Hospital	Odense C
France	Centre Hospitalier Universitaire D'Angers-1	Angers
France	Ap-Hp-Hopital Beaujon	Clichy
France	Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez	Lille
France	Hospices Civils de Lyon-Hopital de La Croix Rousse	Lyon Cedex 4
France	Centre Hospitalier Universitaire de Nice-Hopital de L'Archet 2	Nice
France	Ap-Hp-Hopital Cochin	Paris
France	Aphp-Hopital La Pitie Salpetriere-4	Paris
France	Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1	Pessac
France	Hospices Civils de Lyon-Hopital Lyon Sud-1	Pierre-Benite
France	Les Hopitaux Universitaires de Strasbourg-Hopital Civil-1	Strasbourg Cedex
Germany	Charite Universitätsmedizin Berlin, Virchow-Klinikum	Berlin
Germany	Prof. Dr. Hofmann Wolf-Peter, Berlin	Berlin
Germany	Medizinsche Klinik - Studienbüro Gastroenterologie & Hepatologie Uniklinik Bochum	Bochum
Germany	Dr. Lutz Phillip, Bonn	Bonn
Germany	Hepatologie Universitätsklinikum Frankfurt/M	Frankfurt
Germany	Medizinische Hochschule Hannover, Hepatologie	Hannover
Germany	Prof. Dr. Schiefke Ingolf, EUGASTRO GmbH	Leipzig
Germany	Universitätsklinikum Leipzig, Klinik und Poliklinik	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Otto-von-Guericke University - University Clinic for Gastroenterology, Hepatology and Infectology	Magdeburg
Germany	Universitätsmedizin der Johannes-Gutenberg-Universität Mainz	Mainz
Germany	Universitätsmedizin Mannheim - Studienambulanz, II.Medizinische Klinik	Mannheim
Germany	Universitätsklinikum Würzburg, ZIM	Würzburg
Greece	Gen Hospital of Athens Ippokrateio,B' Uni Clinic of Inte Med	Athens
Greece	Gen Hospital of Athens Laiko,1st Dpt. of Propaedeutic Inter	Athens
Greece	General Hospital of Athens "LAIKO"	Goudi, Athens
Greece	Univ Gen Hospital of Ioannina,Gastroenterology-Endoscopy Uni	Ioannina
Greece	Univ Gen Hospital Larisa, Cardiology Medicine Clinic	Larissa
Greece	"AHEPA" University Hospital of Thessaloniki	Thessaloniki
Greece	AHEPA General University Hospital	Thessaloniki
Greece	General Hospital of Thessaloniki "Ippokrateio"	Thessaloniki
India	Post Graduate Institute of Medical Education & Research_Chandigarh	Chandigarh	Punjab
India	All India Institute of medical Sciences	Delhi	New Delhi
India	Medanta - The Medicity Multi-Speciality Hospital, Gurugram	Gurgaon	Haryana
India	Osmania General Hospital_Hyderabad	Hyderabad	Telangana
India	Ramdev Rao Hospital	Hyderabad	Telangana
India	S.R.Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan
India	SMS Super speciality Hospital, Department of Gastroenterology	Jaipur	Rajasthan
India	MV Hospital and Research Centre	Lucknow	Uttar Pradesh
India	Dayanand Medical College & Hospital	Ludhiana	Punjab
India	Kasturba Medical College Hospitals (KMC Hospitals), Mangalore	Mangalore	Karnataka
India	Fortis Heart Institute and Multispeciality Hospital	Mohali	Punjab
India	Gleneagles Hospital, Super-speciality and Transplant Centre, Parel	Mumbai	Maharashtra
India	Seth GS medical college and KEM Hospital	Mumbai	Maharashtra
India	Midas Multispeciality Hospital	Nagpur	Maharashtra
India	Fortis Escort Heart Institute	New Delhi
India	Institute of liver and Biliary Sciences	New Delhi
India	Yashoda Hospital	Secunderabad	Andhra Pradesh
India	Yashoda Hospital	Secunderabad	Andhra Pradesh
India	BAPS Pramukh Swami Hospital	Surat	Gujarat
India	Surat Institute of Digestive Science	Surat	Gujarat
Ireland	Beaumont Hospital	Dublin
Ireland	Hepatology St James's	Dublin
Israel	Carmel Medical Center Liver Unit	Haifa
Israel	Liver Unit, Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galil Medical Center, Nahariya, Internal Medicine A	Nahariya
Israel	Liver Institute, Rabin Medical Center, Beilinson Campuse	Petah-Tikva
Israel	The Chaim Sheba Medical Center Liver Diseases Center	Ramat-Gan
Israel	Sourasky Medical Center Liver Unit	Tel Aviv
Italy	Azieda Ospedaliero-Universitaria, Policlinico S. Orsola-Malp	Bologna
Italy	Azienda Ospedaliero-Universitaria Renato Dulbecco	Catanzaro	Cz
Italy	AOU Careggi Padiglione 16 San Luca, 3° piano	Firenze
Italy	Ospedali riuniti di Foggia	Foggia
Italy	Osp Magg Policlinico Centro Malattie metaboliche del Fegato	Milano
Italy	AOUP Giaccone Palermo	Palermo
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Policlinico Università Campus Biomedico di Roma	Rome
Italy	IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo	San Giovanni Rotondo	Foggia
Italy	Città della salute e della scienza - university of Torino	Torino
Japan	Juntendo University Hospital, Gastroenterology	Bunkyo-ku, Tokyo
Japan	The University of Tokyo Hospital, Gastroenterology	Bunkyo-ku, Tokyo
Japan	Fukui-ken Saiseikai Hospital, Internal Medicine	Fukui-shi, Fukui
Japan	Hoshi General Hospital_Gastroenterology	Fukushima
Japan	Gifu Municipal Hospital_Hepatology	Gifu
Japan	Ogaki Municipal Hospital_Gastroenterology and Hepatology	Gifu
Japan	Hamamatsu University Hospital	Hamamatsu-shi, Shizuoka
Japan	JA Hiroshima General Hospital	Hatsukaichi-shi, Hiroshima
Japan	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hosp.	Hiroshima-shi, Hiroshima
Japan	Hiroshima University Hospital	Hiroshima-shi, Hiroshima
Japan	Juntendo University Shizuoka Hospital	Izunokuni-shi, Shizuoka
Japan	Kagoshima University Hospital, Gastroenterology	Kagoshima-shi, Kagoshima
Japan	University Hospital Kyoto Prefectual University of Medicine	Kamigyo-ku, Kyoto
Japan	Kanazawa University Hospital	Kanazawa-shi, Ishikawa
Japan	Nara Medical University Hospital_Kashihara-shi, Nara	Kashihara-shi, Nara
Japan	St. Marianna University School of Medicine Hospital	Kawasaki-shi, Kanagawa
Japan	Kumamoto Shinto General Hospital	Kumamoto-shi, Kumamoto
Japan	Toranomon Hospital, Hepatology	Minato-ku, Tokyo
Japan	Japanese Red Cross Musashino Hospital	Musashino-shi, Tokyo
Japan	Aichi Medical University Hospital	Nagakute-shi, Aichi
Japan	Heartlife Hospital	Nakagamigun, Okinawa
Japan	Nara City Hospital, Gastroenterology and Hepatology	Nara-shi, Nara
Japan	Hyogo Medical University Hospital_Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine	Nishinomiya-shi, Hyogo
Japan	Oita Cardiovascular Hospital	Oita-shi, Oita
Japan	Kawasaki Medical School General Medical Center	Okayama-shi, Okayama
Japan	Japan Organization of Occupational Health and Safety Osaka Rosai Hospital_Gastroenterology	Osaka
Japan	Osaka City University Hospital, Department of Hepatology	Osaka-shi, Osaka
Japan	Otsu City Hospital, Gastroenterological Medicine	Otsu-shi, Shiga
Japan	Saga University Hospital_Liver Center	Saga-shi, Saga
Japan	Japan Community Health care Organization Hokkaido Hospital	Sapporo-shi, Hokkaido
Japan	Sendai Kousei Hospital	Sendai-shi, Miyagi
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku, Tokyo
Japan	Osaka University Hospital, Department of Gastro. & Hepato	Suita-shi, Osaka
Japan	Saiseikai Suita Hospital, Gastroenterology	Suita-shi, Osaka
Japan	Kagawa Prefectural Central Hospital	Takamatsu-shi, Kagawa
Japan	National Hospital Organization Takasaki General Medical Ctr.	Takasaki-shi, Gunma
Japan	Nihon University Itabashi Hospital	Tokyo
Japan	Ehime University Hospital	Toon-shi, Ehime
Japan	Saiseikai Wakayama Hospital	Wakayama-shi, Wakayama
Japan	Yokohama City University Hospital, Gastrointestinal Medicine	Yokohama-shi, Kanagawa
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam Univ. Medical Center	Daegu
Korea, Republic of	Wonju Severance Christian Hospital	Gangwon-do
Korea, Republic of	SoonChunHyang University Hospital Bucheon	Gyeonggi-do
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Malaysia	Hospital Selayang	Batu Caves
Malaysia	Hospital Universiti Sains Malaysia	Kota Bharu	Kelantan
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan Kuala Lumpur
Mexico	Centro de Investigacion Clinica del Pacifico, S.A. de C.V.	Acapulco de Juarez	Guerrero
Mexico	Centro de Investigación y Gastroenterología, S.C.	Ciudad de México	México, D.F.
Mexico	Hospital Angeles de Culiacan	Culiacan	Sinaloa
Mexico	Centro de Investigación Médico Biológica y Terapia	Guadalajara	Jalisco
Mexico	Medical Care and Research S. A de C.V	Merida	Yucatan
Mexico	Centro de Investigación y Gastroenterología_ Hospital Angeles Universidad	Mexico
Mexico	Investigaciones Médicas Cisneros, S.C.	Monterrey	Nuevo León
Mexico	Servicios de Oncologia Medica Integral S.A de C.V (ONCARE)	San Pedro Garza Garcia	Nuevo Leon
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Franciscus Gasthuis en Vlietland	Rotterdam
Norway	Bærum sykehus	Gjettum
Norway	Oslo universitetssykehus, Ullevål	Oslo
Poland	Gizinscy Centrum Medyczne	Bydgoszcz
Poland	ID Clinic Arkadiusz Pisula	Myslowice	Malopolskie
Poland	Ko-Med Centra Kliniczne Staszow	Staszow	Swietokrzyskie
Poland	Velocity Nova Sp. z o.o.	Staszow
Poland	BodyClinic	Warszawa
Poland	Centrum Badan Klinicznych	Wroclaw
Poland	FutureMeds Sp. z o.o.	Wroclaw
Portugal	Hospital Garcia de Orta	Almada
Portugal	Hospital Infante D. Pedro - Aveiro	Aveiro
Portugal	Hospital de Braga	Braga
Portugal	Hospital Sousa Martins - Unidade Local de Saúde de Guarda	Guarda
Portugal	Hospital da Senhora da Oliveira - Guimarães	Guimarães
Portugal	APDP - Associação Protectora dos Diabéticos de Portugal	Lisboa
Portugal	Centro Hospitalar Lisboa Norte	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos	Matosinhos
Portugal	Centro Hospitalar de São João	Porto
Portugal	Unidade Local de Saúde de Santo António, E.P.E	Porto
Portugal	Unidade Local de Saúde do Alto Minho - Viana do Castelo	Viana do Castelo
Portugal	Centro Hospitalar Vila Nova de Gaia/Espinho, EPE	Vila Nova de Gaia
Portugal	Hospital da Luz Arrabida	Vila Nova de Gaia
Portugal	Centro Hospitalar de Trás-os-Montes e Alto Douro	Vila Real
Puerto Rico	FDI Clinical Research	San Juan
Romania	Sana Monitoring SRL	Bucharest
Romania	Hightech Medical Services S.R.L.	Bucuresti
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucuresti
Romania	Institutul Gastroenterologie-Hepatologie Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic CF Cluj Napoca	Cluj-Napoca
Romania	Gastroenterologie Spitalul Judetean Constanta	Constanta
Romania	SC Diamed Obesity SRL	Galati
Romania	Gastromedica	Iasi
Romania	County Emergency Hospital Satu Mare	Satu Mare
Russian Federation	Volosevich First City Clinical Hospital	Arkhangelsk
Russian Federation	City Hospital #5	Barnaul
Russian Federation	Kazan Federal University	Kazan
Russian Federation	LLC "Clinic of Aesthetic Medicine & Laser Technologies"	Kazan
Russian Federation	Friendship University of Russia	Moscow
Russian Federation	PHI "Central Clinical Hospital RZD- Medicine"	Moscow
Russian Federation	Setchenov First Moscow State Medical University	Moscow
Russian Federation	Limited Law Company "Healthy Family" Medicine Center"	Novosibirsk
Russian Federation	Penza Regional Clinical Hospital named after N.N. Burdenko	Penza
Russian Federation	Joint Stock Company "Polyclinic Complex"	Saint Petersburg
Russian Federation	SPb SBHI City Outpatient clinic #109	Saint Petersburg
Russian Federation	Consultative & Diagnostic Center with a Outpatient Hospital	Saint-Petersburg
Russian Federation	Limited Liability Company "Energiya Zdoroviya"	Saint-Petersburg
Russian Federation	North-Western State Medical Univer. based on Med-Prof Center	Saint-Petersburg
Russian Federation	North-Western State Medical Univer. based on Med-Prof Center	Saint-Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Russian Federation	Ulianovsk Regional Clinical Hospital	Ulianovsk
Russian Federation	Polyclinic #2 in Yoshkar-Ola	Yoshkar-Ola
Serbia	Clinic for gastroenterology and hepatology	Belgrade
Serbia	Clinical-hospital centre Zvezdara	Belgrade
Serbia	Endocrinology, Diabetes and Metabolism Diseases Clinic	Belgrade
Serbia	Clin. Centre Vojvodina, Clin. endocr., diab. and met. dis.	Novi Sad	Vojvodina
Singapore	Changi General Hospital	Singapore
Singapore	National University Hospital_TBD	Singapore
Singapore	National University Hospital_TBD	Singapore
Singapore	Singapore General Hospital	Singapore
Slovakia	Diabetologická ambulancia - Nemocnica akademika L. Derera, UNB	Bratislava
Slovakia	MEDISPEKTRUM s.r.o.	Bratislava
Slovakia	II. Interna klinika, Univerzitna nemocnica L. Pasteura Kosice	Kosice
Slovakia	Hepatobiliarne centrum - Michalovce	Michalovce
Slovakia	JAL s.r.o.	Trnava
South Africa	Dr Rajabally's Practice	Cape Town	Western Cape
South Africa	Tiervlei Trial Centre	Cape Town	Western Cape
South Africa	Maxwell Centre	Durban	KwaZulu-Natal
South Africa	Maxwell Centre	Durban	KwaZulu-Natal
South Africa	Chris Hani Baragwanath Hospital	Johannesburg	Gauteng
South Africa	Chris Hani Baragwanath Hospital	Johannesburg	Gauteng
South Africa	WITS Clinical Research	Johannesburg	Gauteng
South Africa	Wits Health Consortium	Johannesburg
South Africa	Lenasia Clinical Trial Centre	Lenasia	Gauteng
South Africa	Phoenix Pharma	Port Elizabeth	Eastern Cape
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Complejo Hospitalario de Pontevedra - Hospital de Montecelo	Pontevedra
Spain	Complejo Hospitalario de Pontevedra - Hospital de Montecelo	Pontevedra	Galicia
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital General de Valencia	Valencia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Clínico de Valladolid	Valladolid
Switzerland	Universitätsklinik für Viszerale Chirurgie und Medizin	Bern
Switzerland	Hôpitaux Universitaires de Genève	Geneva
Switzerland	Hôpitaux Universitaires de Genève	Geneva
Switzerland	Kantonsspital Olten	Olten
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	USZ Klinik für Gastroenterologie und Hepatologie	Zürich
Taiwan	Ditmanson Medical Foundation Chia-Yi Christian Hospital	Chiayi City
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaoshiung
Taiwan	Taipei Tzu Chi Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan City
Taiwan	Cathay General Hospital	Taipei
Taiwan	Mackay Memorial Hospital- Taipei	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital	Taipei city
Taiwan	Taipei-Veterans General Hospital - Dept of Gastrointestinal	Taipei city
Turkey	T.C. Saglik Bakanligi Adana Sehir Egitim ve Arastirma Hastan	Adana
Turkey	Ankara Sehir Hastanesi,Gastroenteroloji Klinigi	Ankara
Turkey	Ankara Universitesi Tip Fakultesi Gastroenteroloji Bilim Da	Ankara
Turkey	Hacettepe Universitesi Tip Fakültesi- Gastroenteroloji	Ankara
Turkey	Uludag Universitesi Tip Fakultesi-Gastroenteroloji	Bursa
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi-Gastroe	Istanbul
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi-Gastroenterolog	Istanbul
Turkey	Koc Universitesi Hastanesi-Gastroenteroloji	Istanbul
Turkey	Marmara Univ. Pendik Gastroenterology	Istanbul
Turkey	Umraniye Egitim ve Arastirma Hastanesi, Gastroenteroloji	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi, Gastroenteroloji	Izmir
Turkey	Ege Universitesi Tip Fakultesi Hastanesi, Gastroenteroloji	Izmir
Turkey	Kocaeli Universitesi Tip Fakültesi Gastroenteroloji ve Hepat	Kocaeli
Turkey	Mersin Universitesi Tip Fakultesi Gastroenteroloji Bilim Dal	Mersin
United Kingdom	Royal Victoria Hospital	Belfast
United Kingdom	New Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	WISDEM Centre	Coventry
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Royal Devon University Healthcare NHS Foundation Trust	Exeter
United Kingdom	Hull Royal Infirmary_Hull	Hull
United Kingdom	The Diabetes Centre	Ipswich
United Kingdom	St. James University Hospital	Leeds
United Kingdom	Chelsea & Westminster Hospital	London
United Kingdom	Imperial College London	London
United Kingdom	Liver Research	London
United Kingdom	Royal Free - Immunity & Transplantation	London
United Kingdom	Royal London Hospital_London	London
United Kingdom	Freeman Hospital, Newcastle	Newcastle-Upon Tyne
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Northern General Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Joint Clinical Research Facility - Swansea	Swansea
United States	Amarillo Center for Clinical Research, Ltd.	Amarillo	Texas
United States	University of Michigan Medicine	Ann Arbor	Michigan
United States	Texas Clin Res Inst, LLC	Arlington	Texas
United States	Emory University Hospital	Atlanta	Georgia
United States	Mercy Medical Center, GI Research	Baltimore	Maryland
United States	Walter Reed Nat Mil Md Ctr	Bethesda	Maryland
United States	Boston Medical Center_Cary	Boston	Massachusetts
United States	Encore Medical Research of Boynton Beach LLC	Boynton Beach	Florida
United States	OM Research LLC	Camarillo	California
United States	The Institute for Liver Health	Chandler	Arizona
United States	Medical University Of South Carolina	Charleston	South Carolina
United States	AtriumHealth Liver Care, Pineville	Charlotte	North Carolina
United States	University Of Virginia Hospitl	Charlottesville	Virginia
United States	WR-ClinSearch, LLC	Chattanooga	Tennessee
United States	WR-ClinSearch, LLC	Chattanooga	Tennessee
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Rush University Med. Cntr	Chicago	Illinois
United States	University Of Chicago	Chicago	Illinois
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Peak Gastro Assoc-Col Springs	Colorado Springs	Colorado
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Ohio State Univ Wexner Med Ctr	Columbus	Ohio
United States	Northeast GI Research Division	Concord	North Carolina
United States	Clinical Res Collaborative	Cumberland	Rhode Island
United States	Liver Ins@ Mthdist DTX Med Cen	Dallas	Texas
United States	UT Southwestern Med Cntr	Dallas	Texas
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Geisinger Clinic	Danville	Pennsylvania
United States	Henry Ford Health System	Detroit	Michigan
United States	Integrity Clinical Research, LLC	Doral	Florida
United States	Duke Univ. Med CNTR_Durham_2	Durham	North Carolina
United States	South Texas Research Institute	Edinburg	Texas
United States	Gastroenterology & Liver Institute	Escondido	California
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	AIG Digestive Disease Research	Florham Park	New Jersey
United States	Covenant Metabolic Specialists, Ft. Myers	Fort Myers	Florida
United States	Brooke Army Medical Ctr.	Fort Sam Houston	Texas
United States	GI Alliance Research	Fort Worth	Texas
United States	University of Florida-CTRB	Gainesville	Florida
United States	Woodholme Gastroenterology Associates	Glen Burnie	Maryland
United States	Shang Wu M.D. Inc.	Hacienda Heights	California
United States	Digestive Health Res-TSMC	Hermitage	Tennessee
United States	Pennsylvania State University	Hershey	Pennsylvania
United States	Direct Helpers Research Center	Hialeah	Florida
United States	Miguel Rebollar PA	Hialeah	Florida
United States	Tandem Clinical Research - Houma	Houma	Louisiana
United States	Amir Ali Hassan, MD, PA	Houston	Texas
United States	Baylor College Of Medicine	Houston	Texas
United States	Biopharma Informatic	Houston	Texas
United States	Bipharma Informatic Inc.	Houston	Texas
United States	Bylr Coll Md-Ben Taub Gen Hos	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Research Institute	Houston	Texas
United States	North AL Health Res, LLC	Huntsville	Alabama
United States	Indiana University Hospital	Indianapolis	Indiana
United States	Southern Therapy and Advanced Research LLC	Jackson	Mississippi
United States	East Tennessee Research Institute	Johnson City	Tennessee
United States	ARcare Center for Clinical Research	Jonesboro	Arkansas
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University Of Kansas Hospital	Kansas City	Kansas
United States	Scripps Whittier Diabetes Inst	La Jolla	California
United States	UCSD NAFLD Research Center	La Jolla	California
United States	Florida Research Institute, LLC	Lakewood Ranch	Florida
United States	OM Research LLC	Lancaster	California
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Sierra Clinical Research-Las Vegas	Las Vegas	Nevada
United States	Ocean St Clin Res Partnrs, LLC	Lincoln	Rhode Island
United States	Arkansas Diagnostic Center, PA	Little Rock	Arkansas
United States	Digestive Hlth Res of SoCa	Long Beach	California
United States	Gastroenterology Assoc_ CGA	Macon	Georgia
United States	Sandhill Research, LLC	Maitland	Florida
United States	Tandem Clinical Research - Maitland	Maitland	Florida
United States	Gastroint Spec of Georgia	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Centex Studies - McAllen	McAllen	Texas
United States	Tandem Clinical Research - Metairie	Metairie	Louisiana
United States	Genoma Research Group, Inc	Miami	Florida
United States	IMIC Inc	Miami	Florida
United States	Optimus U, Corp	Miami	Florida
United States	Univ of Miami/Schiff Ctr	Miami	Florida
United States	San Marcus Res Clin Miami Lakes	Miami Lakes	Florida
United States	Quality Medical Research	Nashville	Tennessee
United States	Yale Ctr for Clin Invest	New Haven	Connecticut
United States	Icahn Sch of Med-Mt Sinai Hosp	New York	New York
United States	NYU Grossman School of Med	New York	New York
United States	Weill Cornell Med Coll-NYPH	New York	New York
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Ocala GI Research	Ocala	Florida
United States	Sensible Healthcare LLC	Ocoee	Florida
United States	South Ogden Family Medicine/ CCT Research	Ogden	Utah
United States	Univ of Nebraska Medical CTR	Omaha	Nebraska
United States	Cedars-Sinai Medical Center	Pasadena	California
United States	Pasedena Liver Center	Pasadena	California
United States	LinQ Research, LLC	Pearland	Texas
United States	Inst-Liver Hlth dba AZ Liver H	Peoria	Arizona
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	UPMC Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	UPMC_Center for Liver Care	Pittsburgh	Pennsylvania
United States	Care Access Research, Pottsville	Pottsville	Pennsylvania
United States	Inland Empire Clin Trials LLC	Rialto	California
United States	Bon Secours Richmond Community Hospital LLC	Richmond	Virginia
United States	McGuire VA Medical Center	Richmond	Virginia
United States	VCU Health System	Richmond	Virginia
United States	Velocity Clinical Research, Riverton	Riverton	Utah
United States	Gastroent Consult of SW VA	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Hlth -Midtwn Ambu Cen	Sacramento	California
United States	Theia Clinical Research Centers LLC	Saint Petersburg	Florida
United States	University of Utah	Salt Lake City	Utah
United States	Amer. Rrsch Corp-TX Liver Inst	San Antonio	Texas
United States	Clinical Trials of Texas, LLC	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Silicon Valley Res Inst	San Jose	California
United States	Covenant Metabolic Specialists LLC	Sarasota	Florida
United States	Headlands Research - Sarasota	Sarasota	Florida
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	NorthShore Univ Hlth Sys	Skokie	Illinois
United States	Digestive Research Alliance of Michiana	South Bend	Indiana
United States	Premier Health Research, LLC	Sparta	New Jersey
United States	Objective GI	Springboro	Ohio
United States	Mt Olympus Medical Research, LLC	Sugar Land	Texas
United States	Kansas Medical Clinic, PA	Topeka	Kansas
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Inst. Liver H II dba AZ Liver H	Tucson	Arizona
United States	Options Health Research, LLC	Tulsa	Oklahoma
United States	ClinCloud, LLC	Viera E.	Florida
United States	CRIOH	Westlake	Ohio
United States	Digestive Hlth Res of N Texas	Wichita Falls	Texas
United States	Florida Medical Clinic, LLC	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  Czechia,  Denmark,  France,  Germany,  Greece,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Primary	Part 1: Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Primary	Part 2: Cirrhosis-free survival (Yes/No)	Count of subject	From randomisation (week 0) to week 240
Secondary	Change in body weight	Percentage	From randomisation (week 0) to week 72
Secondary	Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Change in SF-36 (Short Form 36) Bodily Pain	Score points	From randomisation (week 0) to week 72
Secondary	Change in body weight	Percentage	From randomisation (week 0) to week 240
Secondary	Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Change in histology-assessed liver collagen proportionate area	Ratio to baseline	From randomisation (week 0) to week 72
Secondary	Worsening in steatohepatitis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Improvement in histology-assessed ballooning (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Improvement in histology-assessed inflammation (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Improvement in histology-assessed steatosis (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	NASH resolution (ballooning of 0, inflammation of 0-1) and above or equal to 2point NAS reduction with no worsening of fibrosis	Count of subject	From randomisation (week 0) to week 72
Secondary	Progression of liver fibrosis in patients with F2 at baseline (Yes/No)	Count of subject	From randomisation (week 0) to week 72
Secondary	Progression of liver fibrosis	Count of subject	From randomisation (week 0) to week 72
Secondary	Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)	Count of subject	From randomisation (week 0) to week 240
Secondary	Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No)	Count of subject	From randomisation (week 0) to week 240
Secondary	Changes in liver stiffness values assessed by transient elastography (FibroScan®)	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in ELF (Enhanced Liver Fibrosis) score	Logarithm	From randomisation (week 0) to week 72 and week 240
Secondary	Change in ALT (alanine aminotransferase)	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in AST (aspartate aminotransferase)	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in CAP (Controlled Attenuation Parameter) values assessed by transient elastography (FibroScan)	Absolute change	From randomisation (week 0) to week 72 and week 240
Secondary	Change in FAST (FibroScan-AST) score	Probability (absolute change)	From randomisation (week 0) to week 72 and week 240
Secondary	Change in Pro-C3 (pro-peptide of type III collagen)	Logarithm	From randomisation (week 0) to week 72 and week 240
Secondary	Change in inflammation assessed by hsCRP (High Sensitive C-Reactive Protein)	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in HbA1c (glycated haemoglobin)	Percentage-points (absolute change)	From randomisation (week 0) to week 72 and week 240
Secondary	Change in triglyceride	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in free fatty acids	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in LDL (low-density lipoprotein) cholesterol	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Change in HDL (High density lipoprotein ) cholesterol	Ratio to baseline	From randomisation (week 0) to week 72 and week 240
Secondary	Time to first MACE(Major Adverse Cardiovascular event ) (composite endpoint)	Days	From randomisation (week 0) to week 240
Secondary	Major cardio-hepatic event-free survival (Yes/No)	Count of subject	From randomisation (week 0) to week 240
Secondary	Changes in SF-36 (Short Form 36 v2.0 acute ) Physical Component Summary	Score points	From randomisation (week 0) to week 72 and week 240
Secondary	Changes in SF-36 Mental Component Summary	Score points	From randomisation (week 0) to week 72 and week 240
Secondary	Change in SF-36 Bodily Pain	Score points	From randomisation (week 0) to week 240
Secondary	Changes in NASH-CHECK Abdominal Pain	Score points	From randomisation (week 0) to week 72 and week 240