A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage
- Conditions
- Non-alcoholic Steatohepatitis
- Interventions
- Drug: Placebo (semaglutide)
- Registration Number
- NCT03987451
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 71
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo (semaglutide) Semaglutide placebo once-weekly Semaglutide Semaglutide Dose escalation to 2.4 mg of semaglutide once-weekly
- Primary Outcome Measures
Name Time Method Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks Week 48 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline Baseline (week 0), Week 48 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.
Percentage of Participants With NASH Resolution After 48 Weeks Week 48 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.
Change From Baseline in Fibrosis-4 Score-Ratio to Baseline Baseline (week 0), Week 48 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.
Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Baseline (week 0), Week 48 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.
Percentage of Participants With Change in The Fibrosis Stage According to The Kleiner Fibrosis Classification Baseline (week 0), Week 48 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.
Percentage of Participants With Change in Hepatocyte Ballooning Baseline (week 0), Week 48 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.
Percentage of Participants With Change in Lobular Inflammation Baseline (week 0), Week 48 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.
Percentage of Participants With Change in Steatosis Baseline (week 0), Week 48 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.
Percentage of Participants With Change in The Steatosis-Activity-Fibrosis (SAF) Activity Component Score Baseline (week 0), Week 48 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.
Change From Baseline in Hepatic Collagen Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in Steatosis (Yes/No) Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in NAS (Yes/No) Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in SAF Activity Component Score (Yes/No) Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in Ishak Fibrosis Score (Yes/No) Baseline (week 0), Week 48 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.
Change From Baseline in Body Weight Baseline (week 0), Week 48 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.
Percentage of Participants With Change in The Ishak Fibrosis Score Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in Fibrosis Stage According to The Kleiner Fibrosis Classification (Yes/No) Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in Hepatocyte Ballooning (Yes/No) Baseline (week 0), Week 48 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.
Percentage of Participants With Improvement in Lobular Inflammation (Yes/No) Baseline (week 0), Week 48 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.
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Baseline (week 0), Week 48 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.
Change From Baseline in Fasting Plasma Glucose (FPG) Baseline (week 0), Week 48 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.
Change From Baseline in Fasting C-peptide-Ratio to Baseline Baseline (week 0), Week 48 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.
Relative Change From Baseline in Body Weight Baseline (week 0), Week 48 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.
Change From Baseline in Waist Circumference Baseline (week 0), Week 48 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.
Change From Baseline in Body Mass Index (BMI) Baseline (week 0), Week 48 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.
Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48 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.
Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48 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.
Change From Baseline in Systolic And Diastolic Blood Pressure Baseline (week 0), Week 48 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.
Change From Baseline in Total Cholesterol-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Triglycerides-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Albumin-Ratio to Baseline Baseline (week 0), Week 48 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.
Changes From Baseline in Thrombocytes-Ratio to Baseline Baseline (week 0), Week 48 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.
Number of Treatment-Emergent Adverse Events (TEAEs) From baseline (week 0) to week 55 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.
Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Direct Bilirubin-Ratio to Baseline Baseline (week 0), Week 48 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.
Change From Baseline in Total Bilirubin-Ratio to Baseline Baseline (week 0), Week 48 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.
Number of Treatment-Emergent Hypoglycaemic Episodes From baseline (week 0) to week 55 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.
Change From Baseline in Pulse Baseline (week 0), Week 48 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.
Trial Locations
- Locations (38)
Texas Clinical Research Institute, LLC
🇺🇸Arlington, Texas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Miami/Schiff Center for Liver Diseases
🇺🇸Miami, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Duke University
🇺🇸Durham, North Carolina, United States
Piedmont Research Institute
🇺🇸Atlanta, Georgia, United States
Altman Clinical Translational Research Institute
🇺🇸La Jolla, California, United States
American Research Corporation at the Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Inland Empire Clinical Trials LLC
🇺🇸Rialto, California, United States
Hôpital Cochin
🇫🇷Paris, France
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Arizona Liver Health
🇺🇸Chandler, Arizona, United States
The Institute for Liver Health dba Arizona Liver Health
🇺🇸Peoria, Arizona, United States
Excel Medical Center Clinical Trials, LLC
🇺🇸Boca Raton, Florida, United States
Digestive Research Alliance of Michiana
🇺🇸South Bend, Indiana, United States
Mercy Medical Center, GI Research
🇺🇸Baltimore, Maryland, United States
Groupe Hospitalier Mutualiste des Portes du Sud
🇫🇷Venissieux, France
Universitätsklinikum Leipzig, Klinik und Poliklinik
🇩🇪Leipzig, Germany
Hepatologie Universitätsklinikum Frankfurt/M
🇩🇪Frankfurt, Germany
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Universitätsmedizin der Johannes-Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Hôpital Beaujon
🇫🇷Clichy, France
Groupe Hospitalier PITIE-SALPETRIERE
🇫🇷Paris, France
Hôpital de la Croix Rousse
🇫🇷Lyon Cedex 4, France
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Quality Medical Research
🇺🇸Nashville, Tennessee, United States
New Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
University of Florida-CTRB
🇺🇸Gainesville, Florida, United States
Liver Research
🇬🇧London, United Kingdom
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
The University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Gastroenterology Center For The Mid-South
🇺🇸Germantown, Tennessee, United States
Freeman Hospital, Newcastle
🇬🇧Newcastle upon Tyne, United Kingdom
Digestive Health Research - Tristar Summit Medical Center
🇺🇸Hermitage, Tennessee, United States
VCU Health Systems
🇺🇸Richmond, Virginia, United States