Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis.

This Trial is Conducted Globally. The Aim of This Trial is to Investigate Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis

Investigation of efficacy and safety of three dose levels of subcutaneous semaglutide once daily versus placebo in subjects with non-alcoholic steatohepatitis

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis; Hepatobiliary Disorders
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novo Nordisk Investigational Site
    • Kingswood, New South Wales, Australia, 2747
      • Novo Nordisk Investigational Site
    • Westmead, New South Wales, Australia, 2145
      • Novo Nordisk Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Novo Nordisk Investigational Site
    • Fitzroy, Victoria, Australia, 3065
      • Novo Nordisk Investigational Site
• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Salzburg, Austria, 5020
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1030
    • Novo Nordisk Investigational Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novo Nordisk Investigational Site
  • Bruxelles, Belgium, 1070
    • Novo Nordisk Investigational Site
  • Edegem, Belgium, 2650
    • Novo Nordisk Investigational Site
  • Gent, Belgium, 9000
    • Novo Nordisk Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1407
    • Novo Nordisk Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Novo Nordisk Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Novo Nordisk Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novo Nordisk Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Novo Nordisk Investigational Site
    • Hamilton, Ontario, Canada, L8S 4K1
      • Novo Nordisk Investigational Site
    • London, Ontario, Canada, N6A 5A5
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M5G 2C4
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M6H 3M1
      • Novo Nordisk Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Novo Nordisk Investigational Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Novo Nordisk Investigational Site
  • Hvidovre, Denmark, 2650
    • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00290
    • Novo Nordisk Investigational Site
• France
  • Besançon, France, 25000
    • Novo Nordisk Investigational Site
  • Clermont-Ferrand, France, 63003
    • Novo Nordisk Investigational Site
  • Lyon Cedex 4, France, 69317
    • Novo Nordisk Investigational Site
  • MARSEILLE cedex 08, France, 13285
    • Novo Nordisk Investigational Site
  • Montpellier, France, 34090
    • Novo Nordisk Investigational Site
  • NICE cedex 3, France, 06202
    • Novo Nordisk Investigational Site
  • Paris, France, 75651
    • Novo Nordisk Investigational Site
  • Paris, France, 75571
    • Novo Nordisk Investigational Site
  • Pessac, France, 33604
    • Novo Nordisk Investigational Site
  • Toulouse, France, 31059
    • Novo Nordisk Investigational Site
  • Venissieux, France, 69200
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
  • Athens, Greece, 10676
    • Novo Nordisk Investigational Site
  • Goudi, Athens, Greece, GR-115 27
    • Novo Nordisk Investigational Site
  • Larissa, Greece, GR-41110
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54642
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54621
    • Novo Nordisk Investigational Site
• Japan
  • Asahikawa-shi, Hokkaido, Japan, 078-8510
    • Novo Nordisk Investigational Site
  • Fukui-shi, Fukui, Japan, 918-8503
    • Novo Nordisk Investigational Site
  • Kamigyo-ku, Kyoto, Japan, 602-8566
    • Novo Nordisk Investigational Site
  • Kumamoto-shi, Kumamoto, Japan, 862-8655
    • Novo Nordisk Investigational Site
  • Nagakute-shi, Aichi, Japan, 480-1195
    • Novo Nordisk Investigational Site
  • Nara-shi, Nara, Japan, 630-8305
    • Novo Nordisk Investigational Site
  • Nishinomiya-shi, Hyogo, Japan, 663-8501
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 545-8586
    • Novo Nordisk Investigational Site
  • Otsu-shi, Shiga, Japan, 520-0804
    • Novo Nordisk Investigational Site
  • Saga-shi, Saga, Japan, 849-8501
    • Novo Nordisk Investigational Site
  • Shimonoseki-shi, Yamaguchi, Japan, 750-0061
    • Novo Nordisk Investigational Site
  • Suita-shi, Osaka, Japan, 564-0013
    • Novo Nordisk Investigational Site
  • Suita-shi, Osaka, Japan, 565-0862
    • Novo Nordisk Investigational Site
  • Takamatsu-shi, Kagawa, Japan, 760-8557
    • Novo Nordisk Investigational Site
  • Toyoake-shi, Aichi, Japan, 470-1192
    • Novo Nordisk Investigational Site
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Novo Nordisk Investigational Site
  • Amstelveen, Netherlands, 1186 AM
    • Novo Nordisk Investigational Site
  • Amsterdam, Netherlands, 1105 AZ
    • Novo Nordisk Investigational Site
  • Delft, Netherlands, 2625 AD
    • Novo Nordisk Investigational Site
  • Groningen, Netherlands, 9713 GZ
    • Novo Nordisk Investigational Site
  • Leiden, Netherlands, 2333 ZA
    • Novo Nordisk Investigational Site
  • Maastricht, Netherlands, 6229 HX
    • Novo Nordisk Investigational Site
  • Nijmegen, Netherlands, 6525 GA
    • Novo Nordisk Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Novo Nordisk Investigational Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Novo Nordisk Investigational Site
  • Kazan, Russian Federation, 420012
    • Novo Nordisk Investigational Site
  • Kemerovo, Russian Federation, 650066
    • Novo Nordisk Investigational Site
  • Krasnoyarsk, Russian Federation, 660022
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 123423
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 125367
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 111123
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 121170
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 121293
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630099
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630005
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440026
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194356
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 197110
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194358
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 199226
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 190013
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 195067
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 197342
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410039
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410053
    • Novo Nordisk Investigational Site
  • Stavropol, Russian Federation, 355035
    • Novo Nordisk Investigational Site
  • Stavropol, Russian Federation, 355017
    • Novo Nordisk Investigational Site
  • Tomsk, Russian Federation, 634028
    • Novo Nordisk Investigational Site
  • Ulianovsk, Russian Federation, 432063
    • Novo Nordisk Investigational Site
  • Yoshkar-Ola, Russian Federation, 424004
    • Novo Nordisk Investigational Site
• Spain
  • Madrid, Spain, 28034
    • Novo Nordisk Investigational Site
  • Majadahonda, Spain, 28222
    • Novo Nordisk Investigational Site
  • Santander, Spain, 39008
    • Novo Nordisk Investigational Site
  • Santiago de Compostela, Spain, 15706
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41013
    • Novo Nordisk Investigational Site
  • Valencia, Spain, 46026
    • Novo Nordisk Investigational Site
• Sweden
  • Göteborg, Sweden, 413 45
    • Novo Nordisk Investigational Site
  • Malmö, Sweden, 205 02
    • Novo Nordisk Investigational Site
  • Stockholm, Sweden, 112 81
    • Novo Nordisk Investigational Site
  • Stockholm, Sweden, 14186
    • Novo Nordisk Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Novo Nordisk Investigational Site
  • Birmingham, United Kingdom, B9 5SS
    • Novo Nordisk Investigational Site
  • Bolton, United Kingdom, BL4 0JR
    • Novo Nordisk Investigational Site
  • Cambridge, United Kingdom, CB2 2QQ
    • Novo Nordisk Investigational Site
  • Derby, United Kingdom, DE22 3NE
    • Novo Nordisk Investigational Site
  • Dundee, United Kingdom, DD1 9SY
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Novo Nordisk Investigational Site
  • Glasgow, United Kingdom, G31 2ER
    • Novo Nordisk Investigational Site
  • Hull, United Kingdom, HU3 2GZ
    • Novo Nordisk Investigational Site
  • Leeds, United Kingdom, LS9 7TF
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE5 9RS
    • Novo Nordisk Investigational Site
  • London, United Kingdom, NW3 2QG
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE1 7EH
    • Novo Nordisk Investigational Site
  • Nottingham, United Kingdom, NG7 2UH
    • Novo Nordisk Investigational Site
  • Portsmouth, United Kingdom, PO6 3LY
    • Novo Nordisk Investigational Site
  • Swansea, United Kingdom, SA2 8PP
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Novo Nordisk Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Novo Nordisk Investigational Site
    • Tucson, Arizona, United States, 85712
      • Novo Nordisk Investigational Site
  • California
    • Coronado, California, United States, 92118
      • Novo Nordisk Investigational Site
    • Costa Mesa, California, United States, 92627
      • Novo Nordisk Investigational Site
    • La Mesa, California, United States, 91942
      • Novo Nordisk Investigational Site
    • Los Angeles, California, United States, 90057
      • Novo Nordisk Investigational Site
    • Northridge, California, United States, 91325
      • Novo Nordisk Investigational Site
    • Panorama City, California, United States, 91402
      • Novo Nordisk Investigational Site
    • Rialto, California, United States, 92377
      • Novo Nordisk Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Novo Nordisk Investigational Site
    • Gainesville, Florida, United States, 32610
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Novo Nordisk Investigational Site
    • Lakewood Ranch, Florida, United States, 34211
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33136
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33014
      • Novo Nordisk Investigational Site
    • Ocoee, Florida, United States, 34761
      • Novo Nordisk Investigational Site
    • Sarasota, Florida, United States, 34240
      • Novo Nordisk Investigational Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Novo Nordisk Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Novo Nordisk Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Novo Nordisk Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Novo Nordisk Investigational Site
    • Las Vegas, Nevada, United States, 89106
      • Novo Nordisk Investigational Site
  • New York
    • Manhasset, New York, United States, 11030
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2111
      • Novo Nordisk Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Novo Nordisk Investigational Site
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Novo Nordisk Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77030
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77058
      • Novo Nordisk Investigational Site
    • Rollingwood, Texas, United States, 78746
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Novo Nordisk Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Novo Nordisk Investigational Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial except for protocol described pre-screening activities which require a separate informed consent. - Male or female, aged 18-75 years (both inclusive) (for Japan: male or female aged 20-75 years (both inclusive)) at the time of signing informed consent - Local histological diagnosis of NASH followed by histological confirmation of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening - Histologic evidence of NASH based on central pathologist evaluation of a liver biopsy obtained up to 21 weeks before screening. - NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on central pathologist evaluation Exclusion Criteria: - Known or suspected abuse of alcohol (above 20 g/day for women or above 30 g/day for men), alcohol dependence* or narcotics. (* = assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)) - Diagnosis of type 1 diabetes according to medical records - HbA1c above 10% at screening - History or presence of pancreatitis (acute or chronic) - Calcitonin equal or above 50 ng/L at screening - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative - Body Mass Index (BMI) ≤ 25.0 kg/sqm at the screening visit (visit 1) - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Semaglutide 0,1 mg	Drug: Semaglutide; Once daily administration of semaglutide subcutaneously (s.c., under the skin) in three different doses (0.1 mg, 0.2 mg and 0.4 mg)
EXPERIMENTAL: Semaglutide 0,2 mg	Drug: Semaglutide; Once daily administration of semaglutide subcutaneously (s.c., under the skin) in three different doses (0.1 mg, 0.2 mg and 0.4 mg)
EXPERIMENTAL: Semaglutide 0,4 mg	Drug: Semaglutide; Once daily administration of semaglutide subcutaneously (s.c., under the skin) in three different doses (0.1 mg, 0.2 mg and 0.4 mg)
PLACEBO_COMPARATOR: Placebo 1	Drug: Placebo; Once daily administration subcutaneously ( s.c., under the skin)
PLACEBO_COMPARATOR: Placebo 2	Drug: Placebo; Once daily administration subcutaneously ( s.c., under the skin)
PLACEBO_COMPARATOR: Placebo 3	Drug: Placebo; Once daily administration subcutaneously ( s.c., under the skin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No)	NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	After 72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No)	NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning range: 0-2; lobular inflammation range: 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicate greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3)last contact with participant (for participants lost to follow-up); 4)death.	After 72 weeks
Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS)	Percentage of participants who had worsened, improved or had no change in total NAS from baseline to week 72 is presented. Worsening is defined as an increase of at least 1 in the NAS; Improvement is defined as a decrease of at least 1 in the NAS; while no change corresponds to no change in NAS from baseline to week 72. NAS is calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Change in Steatosis	Percentage of participants who had improved, worsened, or had no change in steatosis from baseline to week 72 is presented. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Change in Lobular Inflammation	Percentage of participants who had improved, worsened, or had no change in lobular inflammation from baseline to week 72 is presented. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Change in Hepatocyte Ballooning	Percentage of participants who had improved, worsened, or had no change in hepatocyte ballooning from baseline to week 72 is presented. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification	Percentage of participants who had improved, worsened, or had no change in fibrosis stage from baseline to week 72 is presented. The degree of fibrosis is described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score	Percentage of participants who had improved, worsened, or had no change in the activity component of the SAF score from baseline to week 72 is presented. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Fibrosis-4 Score	Change in fibrosis-4 score is presented as ratio to baseline. Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: Fibrosis-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A Fibrosis-4 index of < 1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in NAFLD Fibrosis Score (NFS)	Change in NFS from baseline to week 72 is presented. NFS is calculated using formula: NFS = -1.675 + 0.037 * age (years) + 0.094 * body mass index (BMI) (kg/m^2) + 1.13 * hyperglycaemia (yes/no) + 0.99 * Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio + 0.013 × platelet count (*10^9/L) - 0.66 * albumin (g/dL). The score is used to classify the probability of fibrosis. A score a) < -1.5 indicates a low probability, b) > -1.5 to < 0.67 indicates intermediate probability, and a score of c) > 0.67 indicates a high probability of liver fibrosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Alanine Aminotransferase (ALT)	Change in ALT (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Aspartate Aminotransferase (AST)	Change in AST (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Gamma Glutamyl Transferase (GGT)	Change in GGT (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Albumin	Change in albumin (measured as grams per deciliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in International Normalized Ratio (INR)	Change in INR is presented as ratio to baseline. INR is the ratio of measured prothrombin time over normal prothrombin time and it evaluates the extrinsic coagulation pathway (vitamin K dependent clotting factors II; V, VII, IX and X). These clotting factors are synthesised in the liver, thus INR is used as a marker of liver synthesis function. The therapeutic INR range varies, most commonly an INR 2-3 goal, but ranging from 1.5-4.0. Bleeding complications are more likely to occur above an INR value of 4.0. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Enhanced Liver Fibrosis (ELF)	Change in ELF from baseline to week 72 is presented. The ELF discriminant score was derived as a log-linear combination of the markers hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP) and tissue inhibitor of metalloproteinase 1 (TIMP1). ELF score = -7.412 + 0.681 × ln(HA (nanograms per millilitre (ng/mL)) + 0.775 × ln(P3NP (ng/mL)) + 0.494 × ln(TIMP1 (ng/mL)). ELF score: a) < 7.7: no to mild fibrosis; b) ≥ 7.7 - < 9.8: Moderate fibrosis; c) ≥ 9.8 - < 11.3: Severe fibrosis; d) ≥ 11.3: Cirrhosis. A negative change from baseline indicates decreased fibrosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Cytokeratin 18 (CK-18) Fragments	Change in CK-18 fragments (M30, M65) (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in microRNA 122 (miR-122)	Change in miR-122 (measured as 1/microliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Interleukin-1 Receptor (IL-1R) Antagonist	Change in interleukin-1 receptor (IL-1R) antagonist (measured as picograms per milliliter) antagonist is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Monocyte Chemoattractant Protein 1 (MCP-1)	Change in MCP-1 (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Fibroblast Growth Factor 21 (FGF-21)	Change in FGF-21 (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Liver Stiffness Assessed by FibroScan®	Change in liver stiffness (measured as kilopascal (kPa)) assessed by FibroScan® is presented as ratio to baseline. FibroScan® is a specialized ultrasound machine for the liver. It measures fibrosis (scarring) by measuring the stiffness of the liver. It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Liver Steatosis Assessed by FibroScan®	Change in liver steatosis assessed by FibroScan® from baseline to week 72 is presented. FibroScan® is a specialized ultrasound machine for the liver. It measures fibrosis (scarring) and steatosis (fatty change) in the liver. Fatty change is fat building up in the liver cells. To assess liver steatosis, the controlled attenuation parameter (CAP; giving an estimate of ultrasound attenuation ∼3.5 MegaHertz (MHz)) is available with the M probe of the FibroScan. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m, with higher scores indicating higher amount of liver with fatty change. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No)	Percentage of participants with weight loss of greater than or equal to (≥) 5% of baseline body weight at 72 weeks is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death. In the below table, 'Yes' infers percentage of participants who have achieved ≥ 5% weight loss; 'No' infers percentage of participants who have not achieved ≥ 5% weight loss at 72 weeks and 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).	Week 72
Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No)	Pentage of participants with weight loss of ≥ 10% of baseline body weight at 72 weeks is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death. In the below table, 'Yes' infers percentage of participants who have achieved ≥ 10% weight loss; 'No' infers percentage of participants who have not achieved ≥ 10% weight loss at 72 weeks and 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).	Week 72
Change in Body Weight	Change in body weight from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Waist Circumference	Change in waist circumference from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Body Mass Index (BMI)	Change in BMI from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Glycosylated Haemoglobin (HbA1c) (%-Point)	Change in HbA1c (measured as percentage point of HbA1c) from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in HbA1c (Millimoles Per Mole)	Change in HbA1c from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Fasting Plasma Glucose (FPG)	Change in FPG from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Fasting Glucagon	Change in fasting glucagon (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR)	Change in HOMA-IR is presented as ratio to baseline. HOMA-IR was calculated as: Insulin resistance (%) = fasting plasma glucose [mmol/L] x fasting insulin [mmol/L]/ 22.5. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Diastolic Blood Pressure (DBP)	Blood pressure was measured in a sitting position after 5 minutes of rest. Change in DBP from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Systolic Blood Pressure (SBP)	Blood pressure was measured in a sitting position after 5 minutes of rest. Change in SBP from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Total Cholesterol	Change in total cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Low Density Lipoprotein (LDL) Cholesterol	Change in LDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in High Density Lipoprotein (HDL) Cholesterol	Change in HDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Very Low Density Lipoprotein (VLDL) Cholesterol	Change in VLDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Triglycerides	Change in triglycerides (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Free Fatty Acids	Change in free fatty acids (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in High Sensitivity C-reactive Protein (hsCRP)	Change in hsCRP (measured as milligram per liter) from baseline to week 72 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Change in Short Form 36 (SF-36) Score	Change in SF-36 score from baseline to week 72 is presented. SF-36 measures participant's overall health related quality of life (HRQoL). It is a 36-item generic measure of health status and yields 2 summary scores for physical health and mental health, and 8 domain scores (physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional, mental health). The scores 0-100 (where higher scores indicates a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of scores in the 2009 U.S. general population. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 72
Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half lives of semaglutide); 2) end of the in-trial period.	From week 0 to week 79
Number of Treatment-emergent Hypoglycaemic Episodes	Hypoglycaemic episode (blood glucose less than or equal to (<=) 3.9 mmol/L (70 mg/dL) Or greater than (>) 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	From week 0 to week 79
Number of Treatment-emergent Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemic Episodes	Severe or BG confirmed symptomatic hypoglycaemia: episode, severe as per american diabetes association (ADA) classification or BG confirmed by plasma glucose value < 3.1 mmol/L(56mg/dL) with symptoms along with hypoglycaemia. Severe hypoglycaemia: episode requiring assistance of other person to actively administer carbohydrate, glucagon, or take corrective actions. Plasma glucose concentrations may not be available during event, but neurological recovery following return of plasma glucose to normal is sufficient evidence that event was induced by low plasma glucose concentration. Hypoglycaemic episode is treatment emergent if onset of it occurs during on-treatment period: period starting on day of first administration of trial product and ending on day of last dose of trial product+7 days; except for evaluation of AEs; hypoglycaemic episodes for which period ended on date of whatever came first:last dose of trial product + 49 days (7 half-lives of semaglutide); end of in-trial period.	From week 0 to week 79
Number of Treatment-emergent Severe Hypoglycaemic Episodes	Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Hypoglycaemic episode is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	From week 0 to week 79
Number of Participants Discontinuing Treatment Due to Gastrointestinal Adverse Events	Number of participants discontinuing treatment due to gastrointestinal adverse events is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	From week 0 to week 79
Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No)	Number of participants with occurrence of anti-semaglutide antibodies during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with occurrence of anti-semaglutide antibodies and 'No' infers number of participants without anti-semaglutide antibodies during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	From week 0 to week 79
Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No)	Number of participants with anti-semaglutide antibodies with in vitro neutralising effect during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with anti-semaglutide antibodies with in vitro neutralising effect and 'No' infers number of participants without anti-semaglutide antibodies with in vitro neutralising effect during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	From week 0 to week 79
Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No)	Number of participants with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with anti-semaglutide antibodies cross reacting with native GLP-1 and 'No' infers number of participants without anti-semaglutide antibodies cross reacting with native GLP-1 during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	From week 0 to week 79
Number of Participants With Cross-reacting Anti-semaglutide Binding Antibodies With in Vitro Neutralising Effect to Native GLP-1 During and After 72 Weeks Treatment (Yes/No)	Number of participants with cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 and 'No' infers number of participants without cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	From week 0 to week 79
Change in Pulse From Baseline to Week 72	Change in pulse from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Percentage of Participants With Change in Electrocardiogram (ECG)	A 12-lead ECG was performed at baseline (week 0) and week 72 and categorised as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). Percentage of participants in each ECG category at week 0 and week 72 are presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Percentage of Participants With Change in Physical Examination: Cardiovascular System	Percentage of participants with change in physical examination (cardiovascular system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System	Percentage of participants with change in physical examination (central and peripheral nervous system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth	Percentage of participants with change in physical examination (gastrointestinal system including mouth) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: General Appearance	Percentage of participants with change in physical examination (general appearance) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck	Percentage of participants with change in physical examination (head, ears, eyes, nose, throat, neck) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation	Percentage of participants with change in physical examination (lymph node palpation) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Musculoskeletal System	Percentage of participants with change in physical examination (musculoskeletal system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Respiratory System	Percentage of participants with change in physical examination (respiratory system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Skin	Percentage of participants with change in physical examination (skin) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Percentage of Participants With Change in Physical Examination: Thyroid Gland	Percentage of participants with change in physical examination (thyroid gland) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Week -6, week 72
Change in Haematocrit	Change in haematocrit from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Haemoglobin (g/dL)	Change in haemoglobin from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Haemoglobin (mmol/L)	Change in haemoglobin from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Leukocytes	Change in leukocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Thrombocytes	Change in thrombocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Erythrocytes	Change in erythrocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Creatinine (mg/dL)	Change in creatinine (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Creatinine (Umol/L)	Change in creatinine (measured as micro mole per liter (umol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Estimated Glomerular Filtration Rate (eGFR)	Change in eGFR (measured as milliliter/minute/1.732 meter square (mL/min/1.73 m^2)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Creatine Kinase	Change in creatine kinase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Urea	Change in urea (measured as milli mole per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Total Bilirubin (mg/dL)	Change in total bilirubin (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Total Bilirubin (Umol/L)	Change in total bilirubin (measured as micromole per liter (umol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Alkaline Phosphatase	Change in alkaline phosphatase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Ferritin	Change in ferritin (measured as microgram per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Sodium (mEq/L)	Change in sodium (measured as milli equivalent per liter (mEq/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Sodium (mmol/L)	Change in sodium (measured as milli mole per liter (mmol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Potassium (mEq/L)	Change in potassium (measured as mEq/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Potassium (mmol/L)	Change in potassium (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Calcium (mg/dL)	Change in calcium (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Calcium (mmol/L)	Change in calcium (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Amylase	Change in amylase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Lipase	Change in lipase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72
Change in Calcitonin	Change in calcitonin (measured as nanograms per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.	Baseline (week 0), Week 72

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA; NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021 Mar 25;384(12):1113-1124. doi: 10.1056/NEJMoa2028395. Epub 2020 Nov 13.
• Harrison SA, Calanna S, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal A, Sejling AS, Newsome PN. Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. Contemp Clin Trials. 2020 Oct;97:106174. doi: 10.1016/j.cct.2020.106174. Epub 2020 Oct 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 30, 2016
• Primary Completion (ACTUAL): February 13, 2020
• Study Completion (ACTUAL): March 19, 2020

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (ESTIMATE): November 22, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases
• Other Study ID Numbers: NN9931-4296; 2016-000685-39 (EUDRACT_NUMBER); U1111-1179-7464 (OTHER: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to Novo Nordisk disclosure commitment on novonordisk.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No