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

• ClinicalTrials.gov Identifier: NCT02970942
• Recruitment Status: Completed
• First Posted: November 22, 2016
• Results First Posted: April 21, 2021
• Last Update Posted: November 16, 2021
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hepatobiliary Disorders; Non-alcoholic Steatohepatitis	Drug: Semaglutide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 30, 2016
• Actual Primary Completion Date: February 13, 2020
• Actual Study Completion Date: March 19, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) [ Time Frame: After 72 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). 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.

Secondary Outcome Measures :

1. Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No) [ Time Frame: After 72 weeks ]
   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.
2. Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) [ Time Frame: Baseline (week 0), Week 72 ]
   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.
3. Percentage of Participants With Change in Steatosis [ Time Frame: Baseline (week 0), Week 72 ]
   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.
4. Percentage of Participants With Change in Lobular Inflammation [ Time Frame: Baseline (week 0), Week 72 ]
   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.
5. Percentage of Participants With Change in Hepatocyte Ballooning [ Time Frame: Baseline (week 0), Week 72 ]
   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.
6. Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification [ Time Frame: Baseline (week 0), Week 72 ]
   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.
7. Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score [ Time Frame: Baseline (week 0), Week 72 ]
   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.
8. Change in Fibrosis-4 Score [ Time Frame: Baseline (week 0), Week 72 ]
   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.
9. Change in NAFLD Fibrosis Score (NFS) [ Time Frame: Baseline (week 0), Week 72 ]
   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.
10. Change in Alanine Aminotransferase (ALT) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
11. Change in Aspartate Aminotransferase (AST) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
12. Change in Gamma Glutamyl Transferase (GGT) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
13. Change in Albumin [ Time Frame: Baseline (week 0), Week 72 ]
    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.
14. Change in International Normalized Ratio (INR) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
15. Change in Enhanced Liver Fibrosis (ELF) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
16. Change in Cytokeratin 18 (CK-18) Fragments [ Time Frame: Baseline (week 0), Week 72 ]
    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.
17. Change in microRNA 122 (miR-122) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
18. Change in Interleukin-1 Receptor (IL-1R) Antagonist [ Time Frame: Baseline (week 0), Week 72 ]
    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.
19. Change in Monocyte Chemoattractant Protein 1 (MCP-1) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
20. Change in Fibroblast Growth Factor 21 (FGF-21) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
21. Change in Liver Stiffness Assessed by FibroScan® [ Time Frame: Baseline (week 0), Week 72 ]
    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.
22. Change in Liver Steatosis Assessed by FibroScan® [ Time Frame: Baseline (week 0), Week 72 ]
    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.
23. Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No) [ Time Frame: Week 72 ]
    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).
24. Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No) [ Time Frame: Week 72 ]
    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).
25. Change in Body Weight [ Time Frame: Baseline (week 0), Week 72 ]
    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.
26. Change in Waist Circumference [ Time Frame: Baseline (week 0), Week 72 ]
    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.
27. Change in Body Mass Index (BMI) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
28. Change in Glycosylated Haemoglobin (HbA1c) (%-Point) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
29. Change in HbA1c (Millimoles Per Mole) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
30. Change in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
31. Change in Fasting Glucagon [ Time Frame: Baseline (week 0), Week 72 ]
    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.
32. Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
33. Change in Diastolic Blood Pressure (DBP) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
34. Change in Systolic Blood Pressure (SBP) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
35. Change in Total Cholesterol [ Time Frame: Baseline (week 0), Week 72 ]
    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.
36. Change in Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: Baseline (week 0), Week 72 ]
    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.
37. Change in High Density Lipoprotein (HDL) Cholesterol [ Time Frame: Baseline (week 0), Week 72 ]
    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.
38. Change in Very Low Density Lipoprotein (VLDL) Cholesterol [ Time Frame: Baseline (week 0), Week 72 ]
    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.
39. Change in Triglycerides [ Time Frame: Baseline (week 0), Week 72 ]
    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.
40. Change in Free Fatty Acids [ Time Frame: Baseline (week 0), Week 72 ]
    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.
41. Change in High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
42. Change in Short Form 36 (SF-36) Score [ Time Frame: Baseline (week 0), Week 72 ]
    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.
43. Number of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From week 0 to week 79 ]
    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.
44. Number of Treatment-emergent Hypoglycaemic Episodes [ Time Frame: From week 0 to week 79 ]
    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.
45. Number of Treatment-emergent Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: From week 0 to week 79 ]
    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.
46. Number of Treatment-emergent Severe Hypoglycaemic Episodes [ Time Frame: From week 0 to week 79 ]
    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.
47. Number of Participants Discontinuing Treatment Due to Gastrointestinal Adverse Events [ Time Frame: From week 0 to week 79 ]
    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.
48. Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No) [ Time Frame: From week 0 to week 79 ]
    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.
49. Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No) [ Time Frame: From week 0 to week 79 ]
    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.
50. Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No) [ Time Frame: From week 0 to week 79 ]
    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.
51. 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) [ Time Frame: 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 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.
52. Change in Pulse From Baseline to Week 72 [ Time Frame: Baseline (week 0), 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.
53. Percentage of Participants With Change in Electrocardiogram (ECG) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
54. Percentage of Participants With Change in Physical Examination: Cardiovascular System [ Time Frame: Week -6, week 72 ]
    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.
55. Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System [ Time Frame: Week -6, week 72 ]
    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.
56. Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth [ Time Frame: Week -6, week 72 ]
    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.
57. Percentage of Participants With Change in Physical Examination: General Appearance [ Time Frame: Week -6, week 72 ]
    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.
58. Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck [ Time Frame: Week -6, week 72 ]
    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.
59. Percentage of Participants With Change in Physical Examination: Lymph Node Palpation [ Time Frame: Week -6, week 72 ]
    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.
60. Percentage of Participants With Change in Physical Examination: Musculoskeletal System [ Time Frame: Week -6, week 72 ]
    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.
61. Percentage of Participants With Change in Physical Examination: Respiratory System [ Time Frame: Week -6, week 72 ]
    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.
62. Percentage of Participants With Change in Physical Examination: Skin [ Time Frame: Week -6, week 72 ]
    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.
63. Percentage of Participants With Change in Physical Examination: Thyroid Gland [ Time Frame: Week -6, week 72 ]
    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.
64. Change in Haematocrit [ Time Frame: Baseline (week 0), Week 72 ]
    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.
65. Change in Haemoglobin (g/dL) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
66. Change in Haemoglobin (mmol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
67. Change in Leukocytes [ Time Frame: Baseline (week 0), Week 72 ]
    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.
68. Change in Thrombocytes [ Time Frame: Baseline (week 0), Week 72 ]
    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.
69. Change in Erythrocytes [ Time Frame: Baseline (week 0), Week 72 ]
    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.
70. Change in Creatinine (mg/dL) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
71. Change in Creatinine (Umol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
72. Change in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
73. Change in Creatine Kinase [ Time Frame: Baseline (week 0), Week 72 ]
    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.
74. Change in Urea [ Time Frame: Baseline (week 0), Week 72 ]
    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.
75. Change in Total Bilirubin (mg/dL) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
76. Change in Total Bilirubin (Umol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
77. Change in Alkaline Phosphatase [ Time Frame: Baseline (week 0), Week 72 ]
    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.
78. Change in Ferritin [ Time Frame: Baseline (week 0), Week 72 ]
    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.
79. Change in Sodium (mEq/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
80. Change in Sodium (mmol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
81. Change in Potassium (mEq/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
82. Change in Potassium (mmol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
83. Change in Calcium (mg/dL) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
84. Change in Calcium (mmol/L) [ Time Frame: Baseline (week 0), Week 72 ]
    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.
85. Change in Amylase [ Time Frame: Baseline (week 0), Week 72 ]
    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.
86. Change in Lipase [ Time Frame: Baseline (week 0), Week 72 ]
    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.
87. Change in Calcitonin [ Time Frame: Baseline (week 0), Week 72 ]
    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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Alabama

Novo Nordisk Investigational Site

Birmingham, Alabama, United States, 35233

United States, Arizona

Novo Nordisk Investigational Site

Chandler, Arizona, United States, 85224

Novo Nordisk Investigational Site

Tucson, Arizona, United States, 85712

United States, California

Novo Nordisk Investigational Site

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

United States, Florida

Novo Nordisk Investigational Site

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, 33014

Novo Nordisk Investigational Site

Miami, Florida, United States, 33136

Novo Nordisk Investigational Site

Ocoee, Florida, United States, 34761

Novo Nordisk Investigational Site

Sarasota, Florida, United States, 34240

United States, Louisiana

Novo Nordisk Investigational Site

Monroe, Louisiana, United States, 71201

United States, Maryland

Novo Nordisk Investigational Site

Baltimore, Maryland, United States, 21202

United States, Michigan

Novo Nordisk Investigational Site

Detroit, Michigan, United States, 48202

United States, Minnesota

Novo Nordisk Investigational Site

Rochester, Minnesota, United States, 55905

United States, Nebraska

Novo Nordisk Investigational Site

Omaha, Nebraska, United States, 68198

United States, Nevada

Novo Nordisk Investigational Site

Las Vegas, Nevada, United States, 89106

Novo Nordisk Investigational Site

Las Vegas, Nevada, United States, 89109

United States, New York

Novo Nordisk Investigational Site

Manhasset, New York, United States, 11030

United States, Pennsylvania

Novo Nordisk Investigational Site

Danville, Pennsylvania, United States, 17822-2111

Novo Nordisk Investigational Site

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Novo Nordisk Investigational Site

Hermitage, Tennessee, United States, 37076

United States, Texas

Novo Nordisk Investigational Site

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

United States, Vermont

Novo Nordisk Investigational Site

Burlington, Vermont, United States, 05401

United States, Virginia

Novo Nordisk Investigational Site

Richmond, Virginia, United States, 23249

United States, Washington

Novo Nordisk Investigational Site

Seattle, Washington, United States, 98104

Australia, New South Wales

Novo Nordisk Investigational Site

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

Australia, Victoria

Novo Nordisk Investigational Site

Box Hill, Victoria, Australia, 3128

Novo Nordisk Investigational Site

Fitzroy, Victoria, Australia, 3065

Austria

Novo Nordisk Investigational Site

Graz, Austria, 8036

Novo Nordisk Investigational Site

Salzburg, Austria, 5020

Novo Nordisk Investigational Site

Wien, Austria, 1030

Belgium

Novo Nordisk Investigational Site

Bruxelles, Belgium, 1070

Novo Nordisk Investigational Site

Bruxelles, Belgium, 1200

Novo Nordisk Investigational Site

Edegem, Belgium, 2650

Novo Nordisk Investigational Site

Gent, Belgium, 9000

Bulgaria

Novo Nordisk Investigational Site

Sofia, Bulgaria, 1407

Novo Nordisk Investigational Site

Sofia, Bulgaria, 1431

Canada, Alberta

Novo Nordisk Investigational Site

Calgary, Alberta, Canada, T2N 4Z6

Canada, Manitoba

Novo Nordisk Investigational Site

Winnipeg, Manitoba, Canada, R3E 3P4

Canada, Nova Scotia

Novo Nordisk Investigational Site

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

Novo Nordisk Investigational Site

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

Canada, Quebec

Novo Nordisk Investigational Site

Montreal, Quebec, Canada, H4A 3J1

Denmark

Novo Nordisk Investigational Site

Aarhus N, Denmark, 8200

Novo Nordisk Investigational Site

Hvidovre, Denmark, 2650

Finland

Novo Nordisk Investigational Site

Helsinki, Finland, 00290

France

Novo Nordisk Investigational Site

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, 75571

Novo Nordisk Investigational Site

Paris, France, 75651

Novo Nordisk Investigational Site

Pessac, France, 33604

Novo Nordisk Investigational Site

Toulouse, France, 31059

Novo Nordisk Investigational Site

Venissieux, France, 69200

Greece

Novo Nordisk Investigational Site

Athens, Greece, 10676

Novo Nordisk Investigational Site

Athens, Greece, GR-11527

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-54621

Novo Nordisk Investigational Site

Thessaloniki, Greece, GR-54642

Japan

Novo Nordisk Investigational Site

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

Netherlands

Novo Nordisk Investigational Site

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

Puerto Rico

Novo Nordisk Investigational Site

San Juan, Puerto Rico, 00927

Russian Federation

Novo Nordisk Investigational Site

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, 111123

Novo Nordisk Investigational Site

Moscow, Russian Federation, 121170

Novo Nordisk Investigational Site

Moscow, Russian Federation, 121293

Novo Nordisk Investigational Site

Moscow, Russian Federation, 123423

Novo Nordisk Investigational Site

Moscow, Russian Federation, 125367

Novo Nordisk Investigational Site

Novosibirsk, Russian Federation, 630005

Novo Nordisk Investigational Site

Novosibirsk, Russian Federation, 630099

Novo Nordisk Investigational Site

Penza, Russian Federation, 440026

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 190013

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 194356

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 194358

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 195067

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 197110

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 197342

Novo Nordisk Investigational Site

Saint-Petersburg, Russian Federation, 199226

Novo Nordisk Investigational Site

Saratov, Russian Federation, 410039

Novo Nordisk Investigational Site

Saratov, Russian Federation, 410053

Novo Nordisk Investigational Site

Stavropol, Russian Federation, 355017

Novo Nordisk Investigational Site

Stavropol, Russian Federation, 355035

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

Spain

Novo Nordisk Investigational Site

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

Sweden

Novo Nordisk Investigational Site

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

United Kingdom

Novo Nordisk Investigational Site

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, NW3 2QG

Novo Nordisk Investigational Site

London, United Kingdom, SE1 7EH

Novo Nordisk Investigational Site

London, United Kingdom, SE5 9RS

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

Sponsors and Collaborators

Novo Nordisk A/S

  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:

Study Protocol  [PDF] January 9, 2018

Statistical Analysis Plan  [PDF] February 27, 2020

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02970942
• Other Study ID Numbers: NN9931-4296; 2016-000685-39 ( EudraCT Number ); U1111-1179-7464 ( Other Identifier: WHO )
• First Posted: November 22, 2016
• Results First Posted: April 21, 2021
• Last Update Posted: November 16, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to Novo Nordisk disclosure commitment on novonordisk.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Liver Diseases; Semaglutide; Glucagon-Like Peptide-1 Receptor Agonists; Hypoglycemic Agents; Physiological Effects of Drugs