A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage

Investigation of Efficacy and Safety of Semaglutide s.c. Once-weekly Versus Placebo in Subjects With Non-alcoholic Steatohepatitis and Compensated Liver Cirrhosis

Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clichy, France, 92110
    • Hôpital Beaujon
  • Lyon Cedex 4, France, 69317
    • Hôpital de La Croix Rousse
  • Paris, France, 75014
    • Hôpital Cochin
  • Paris, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere
  • Venissieux, France, 69200
    • Groupe Hospitalier Mutualiste Des Portes Du Sud
• Germany
  • Frankfurt, Germany, 60590
    • Hepatologie Universitätsklinikum Frankfurt/M
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig, Klinik und Poliklinik
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes-Gutenberg-Universität Mainz
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • New Queen Elizabeth Hospital Birmingham
  • London, United Kingdom, SE5 9RS
    • Liver Research
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital, Newcastle
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Peoria, Arizona, United States, 85381
      • The Institute for Liver Health DBA Arizona Liver Health
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • La Jolla, California, United States, 92037
      • Altman Clinical Translational Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials LLC
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Center Clinical Trials, LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida-CTRB
    • Miami, Florida, United States, 33136
      • University of Miami/Schiff Center for Liver Diseases
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Research Institute
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • South Bend, Indiana, United States, 46635
      • Digestive Research Alliance of Michiana
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • University of Kentucky Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center, GI Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastroenterology Center For The Mid-South
    • Hermitage, Tennessee, United States, 37076
      • Digestive Health Research - Tristar Summit Medical Center
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Dallas, Texas, United States, 75390-8887
      • The University of Texas Southwestern Medical Center - Dallas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • VCU Health Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
• Histologic evidence of NASH and fibrosis stage 4 according to the NASH CRN classification based on central pathologist evaluation of a liver biopsy obtained within 360 days prior to screening. In subjects who have never had a liver biopsy showing NASH and F4, liver stiffness above 14 kPa by FibroScan® at screening must be documented before subjects can have a trial-related liver biopsy
• A histological NAFLD activity score (NAS) equal to or above 3 with a score of 1 or more in lobular inflammation and hepatocyte ballooning based on central pathologist evaluation
• Body mass index equal to or above 27 kg/m^2

Exclusion Criteria:

• Presence or history of hepatic decompensation (e.g. ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis) or liver transplantation
• Presence or history of gastroesophageal varices within the past 360 days prior to screening. For subjects with no known history of gastroesophageal varices and with a Fibroscan® equal to or above 20 kPa and thrombocytes equal to or below 150,000, a esophagogastroduodenoscopy must be performed to evaluate presence of gastroesophageal varices
• Presence or history of hepatocellular carcinoma
• Treatment with vitamin E (at doses equal to or above 800 IU/day) or pioglitazone which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to screening
• Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the period from 90 days prior to screening
• Treatment with other glucose lowering agent(s) (apart from what is listed in the exclusion criterion above) or weight loss medication not stable in the opinion of the investigator in the period from 28 days prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Dose escalation to 2.4 mg of semaglutide once-weekly	Drug: Semaglutide; Semaglutide given subcutaneously (s.c., under the skin) once-weekly for 48 weeks
Placebo Comparator: Placebo; Semaglutide placebo once-weekly	Drug: Placebo (semaglutide); Semaglutide placebo s.c. given once-weekly for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks	NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline	Change in liver fat content (measured as percentage) from baseline to week 48 is presented as ratio to baseline. Liver fat content was assessed via MRI-PDFF technique and results were measured in percentage. MRI-PDFF utilized a gradient echo sequence with low flip angle to minimize T1 bias, corrected T2* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline	Change in Liver Stiffness from baseline to week 48 is presented as ratio to baseline. Liver stiffness was measured in kilopascal using MRE. MRE is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of the liver. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With NASH Resolution After 48 Weeks	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). Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Week 48
Change From Baseline in Fibrosis-4 Score-Ratio to Baseline	Change in fibrosis-4 score from baseline to week 48 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), aspartate aminotransferase (AST) and age that was calculated using formula: Fibrosis-4 = (Age [years] x AST [units per liter (U/L)]) / (platelets [10^9 cells/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. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)	Percentage of participants who had worsened, improved or had no change in total NAS from baseline to week 48 or missing data is presented. Worsening was defined as an increase of at least 1 in the NAS; Improvement was defined as a decrease of at least 1 in the NAS; while no change corresponds to no change in NAS and missing refers to participants with missing outcomes for NAS from baseline to week 48. NAS was 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. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Change in The 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 48 or missing data is presented. The degree of fibrosis was 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). Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
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 48 or missing data is presented. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
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 48 or missing data is presented. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Change in Steatosis	Percentage of participants who had improved, worsened, or had no change in steatosis from baseline to week 48 or missing data is presented. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Change in The Steatosis-Activity-Fibrosis (SAF) Activity Component Score	Percentage of participants who had improved, worsened, or had no change in the activity component of the SAF score from baseline to week 48 or missing data is presented. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Change in The Ishak Fibrosis Score	Percentage of participants who had improved, worsened, or had no change in the Ishak fibrosis score from baseline to week 48 or missing data is presented. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Hepatic Collagen	Change in hepatic collagen from baseline to week 48 was analysed. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in Fibrosis Stage According to The Kleiner Fibrosis Classification (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in Kleiner fibrosis classification. The degree of fibrosis was 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). Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in Hepatocyte Ballooning (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in hepatocyte ballooning clinical research network (CRN) score. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in Lobular Inflammation (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in lobular inflammation CRN score. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in Steatosis (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in steatosis CRN score. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in NAS (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in NAS. NAS was 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. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in SAF Activity Component Score (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in SAF score. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Improvement in Ishak Fibrosis Score (Yes/No)	Improvement is defined as at least one stage decrease from baseline to week 48 in Ishak fibrosis score. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Body Weight	Change in body weight from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Relative Change From Baseline in Body Weight	Relative change in body weight (measured as kg) from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Waist Circumference	Change in waist circumference from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Body Mass Index (BMI)	Change in BMI from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48	Percentage of participants with weight loss of greater than or equal to (≥) 5% of baseline body weight at 48 weeks is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Week 48
Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48	Percentage of participants with weight loss of ≥ 10% of baseline body weight at 48 weeks is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Week 48
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c)	Change in HbA1c from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Fasting Plasma Glucose (FPG)	Change in FPG from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Fasting C-peptide-Ratio to Baseline	Change in fasting C-peptide [measured as nanomoles per litre (nmol/L)] from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Systolic And Diastolic Blood Pressure	Change in systolic and diastolic blood pressure from baseline to week 48 is presented. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Total Cholesterol-Ratio to Baseline	Change in total cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline	Change in LDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline	Change in HDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline	Change in VLDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Triglycerides-Ratio to Baseline	Change in triglycerides (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline	Change in free fatty acids (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	Change in hsCRP (measured as milligrams per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline	Change in ALT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline	Change in AST (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline	Change in GGT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Albumin-Ratio to Baseline	Change in albumin [measured as grams per deciliter (g/dL)] from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Changes From Baseline in Thrombocytes-Ratio to Baseline	Change in thrombocytes [measured as 10^9 cells per liter] from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline	Change in INR from baseline to week 48 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. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Direct Bilirubin-Ratio to Baseline	Change in direct bilirubin [measured as micromoles per liter (umol/L)] from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
Change From Baseline in Total Bilirubin-Ratio to Baseline	Change in total bilirubin [measured as umol/L] from baseline to week 48 is presented as ratio to baseline. Outcome measure 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 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.	Baseline (week 0), Week 48
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. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.	From baseline (week 0) to week 55
Number of Treatment-Emergent Hypoglycaemic Episodes	Hypoglycaemic episode (blood glucose less than or equal to (<=) 3.9 mmol/L [70 milligrams per decilitre (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. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.	From baseline (week 0) to week 55
Change From Baseline in Pulse	Change in pulse from baseline to week 48 is presented. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.	Baseline (week 0), Week 48

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• Loomba R, Abdelmalek MF, Armstrong MJ, Jara M, Kjaer MS, Krarup N, Lawitz E, Ratziu V, Sanyal AJ, Schattenberg JM, Newsome PN; NN9931-4492 investigators. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Jun;8(6):511-522. doi: 10.1016/S2468-1253(23)00068-7. Epub 2023 Mar 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2019
• Primary Completion (Actual): April 22, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: NN9931-4492; U1111-1224-4062 (Other Identifier: World Health Organization (WHO)); 2018-004484-31 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

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