Phase 2
Completed N=71
A Research Study on How Semaglutide Works in People With Fatty Liver Disease and Liver Damage
Source: ClinicalTrials.gov NCT03987451 ↗Enrolled (actual)
71
Serious AEs
11.3%
Results posted
May 2024
Primary outcomePrimary: Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks — 10.6; 29.2 Percentage of participants — p=0.0867
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks |
10.6; 29.2 | 0.0867 |
| SECONDARY Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline |
0.62; 1.01 | — |
| SECONDARY Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline |
0.87; 0.98 | — |
| SECONDARY Percentage of Participants With NASH Resolution After 48 Weeks |
34.0; 20.8 | — |
| SECONDARY Change From Baseline in Fibrosis-4 Score-Ratio to Baseline |
0.9; 1.0 | — |
| SECONDARY Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) |
61.7; 58.3; 2.1; 16.7; 21.3; 20.8 | — |
| SECONDARY Percentage of Participants With Change in The Fibrosis Stage According to The Kleiner Fibrosis Classification |
12.8; 33.3; 0.0; 0.0; 72.3; 62.5 | — |
| SECONDARY Percentage of Participants With Change in Hepatocyte Ballooning |
55.3; 33.3; 2.1; 8.3; 27.7; 54.2 | — |
| SECONDARY Percentage of Participants With Change in Lobular Inflammation |
42.6; 37.5; 12.8; 12.5; 29.8; 45.8 | — |
| SECONDARY Percentage of Participants With Change in Steatosis |
44.7; 33.3; 2.1; 16.7; 38.3; 45.8 | — |
| SECONDARY Percentage of Participants With Change in The Steatosis-Activity-Fibrosis (SAF) Activity Component Score |
57.4; 50.0; 8.5; 12.5; 19.1; 33.3 | — |
| SECONDARY Percentage of Participants With Change in The Ishak Fibrosis Score |
27.7; 37.5; 2.1; 12.5; 55.3; 45.8 | — |
| SECONDARY Change From Baseline in Hepatic Collagen |
-1.7; -1.2 | — |
| SECONDARY Percentage of Participants With Improvement in Fibrosis Stage According to The Kleiner Fibrosis Classification (Yes/No) |
12.8; 33.3; 72.3; 62.5; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in Hepatocyte Ballooning (Yes/No) |
55.3; 33.3; 29.8; 62.5; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in Lobular Inflammation (Yes/No) |
42.6; 37.5; 42.6; 58.3; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in Steatosis (Yes/No) |
44.7; 33.3; 40.4; 62.5; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in NAS (Yes/No) |
61.7; 58.3; 23.4; 37.5; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in SAF Activity Component Score (Yes/No) |
57.4; 50.0; 27.7; 45.8; 14.9; 4.2 | — |
| SECONDARY Percentage of Participants With Improvement in Ishak Fibrosis Score (Yes/No) |
27.7; 37.5; 57.4; 58.3; 14.9; 4.2 | — |
| SECONDARY Change From Baseline in Body Weight |
-8.6; -0.8 | — |
| SECONDARY Relative Change From Baseline in Body Weight |
-8.83; -0.09 | — |
| SECONDARY Change From Baseline in Waist Circumference |
-6.3; 0.4 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) |
-3.1; -0.2 | — |
| SECONDARY Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48 |
62.0; 25.4 | — |
| SECONDARY Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48 |
40.5; 0 | — |
| SECONDARY Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) |
-1.4; 0.2 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) |
-2.20; 0.23 | — |
| SECONDARY Change From Baseline in Fasting C-peptide-Ratio to Baseline |
0.95; 1.00 | — |
| SECONDARY Change From Baseline in Systolic And Diastolic Blood Pressure |
-4.1; 0.1; 0.4; -0.7 | — |
| SECONDARY Change From Baseline in Total Cholesterol-Ratio to Baseline |
0.98; 1.05 | — |
| SECONDARY Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline |
0.99; 1.02 | — |
| SECONDARY Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline |
1.07; 0.99 | — |
| SECONDARY Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline |
0.90; 1.09 | — |
| SECONDARY Change From Baseline in Triglycerides-Ratio to Baseline |
0.90; 1.09 | — |
| SECONDARY Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline |
1.07; 1.43 | — |
| SECONDARY Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline |
0.63; 1.13 | — |
| SECONDARY Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline |
0.7; 1.0 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline |
0.7; 1.0 | — |
| SECONDARY Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline |
0.7; 1.0 | — |
| SECONDARY Change From Baseline in Albumin-Ratio to Baseline |
1.0; 1.0 | — |
| SECONDARY Changes From Baseline in Thrombocytes-Ratio to Baseline |
1.0; 1.0 | — |
| SECONDARY Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline |
1.02; 1.01 | — |
| SECONDARY Change From Baseline in Direct Bilirubin-Ratio to Baseline |
1.1; 1.0 | — |
| SECONDARY Change From Baseline in Total Bilirubin-Ratio to Baseline |
1.0; 0.9 | — |
| SECONDARY Number of Treatment-Emergent Adverse Events (TEAEs) |
290; 85 | — |
| SECONDARY Number of Treatment-Emergent Hypoglycaemic Episodes |
34; 15 | — |
| SECONDARY Change From Baseline in Pulse |
6; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
- Histologic evidence of NASH and fibrosis stage 4 according to the NASH CRN classification based on central pathologist evaluation of a liver biopsy obtained within 360 days prior to screening. In subjects who have never had a liver biopsy showing NASH and F4, liver stiffness above 14 kPa by FibroScan® at screening must be documented before subjects can have a trial-related liver biopsy
- A histological NAFLD activity score (NAS) equal to or above 3 with a score of 1 or more in lobular inflammation and hepatocyte ballooning based on central pathologist evaluation
- Body mass index equal to or above 27 kg/m^2
Exclusion Criteria
- Presence or history of hepatic decompensation (e.g. ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis) or liver transplantation
- Presence or history of gastroesophageal varices within the past 360 days prior to screening. For subjects with no known history of gastroesophageal varices and with a Fibroscan® equal to or above 20 kPa and thrombocytes equal to or below 150,000, a esophagogastroduodenoscopy must be performed to evaluate presence of gastroesophageal varices
- Presence or history of hepatocellular carcinoma
- Treatment with vitamin E (at doses equal to or above 800 IU/day) or pioglitazone which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to screening
- Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the period from 90 days prior to screening
- Treatment with other glucose lowering agent(s) (apart from what is listed in the exclusion criterion above) or weight loss medication not stable in the opinion of the investigator in the period from 28 days prior to screening
Data sourced from ClinicalTrials.gov (NCT03987451). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.