Non-alcoholic steatohepatitis MedDRA version: 24.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age above or equal to 18 years at the time of signing informed consent. - Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to the screening visit (V1). - Histological evidence of fibrosis stage 2 or stage 3 according to the NASH Clinical Research Network (CRN) classification based on a central pathologist evaluation of the baseline liver biopsy. - A histological NAS = 4 with a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 960 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: • Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD) • Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A). • Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation. • Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)). • Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in from time of biopsy until screening. • Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening (V2A). • Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Part 1: To demonstrate that treatment with semaglutide 2.4 mg administered subcutaneously (under the skin, s.c.) improves liver histology compared to placebo in subjects with NASH and fibrosis stage 2 or 3. 2. Part 2: To demonstrate that treatment with semaglutide s.c. 2.4 mg lowers the risk of liver-related clinical events compared to placebo in subjects with NASH and fibrosis stage 2 or 3.;Secondary Objective: 1. To demonstrate that treatment with semaglutide s.c. 2.4 mg lowers body weight compared to placebo in subjects with NASH and fibrosis stages 2 or 3. 2. To demonstrate that treatment with semaglutide s.c. 2.4 mg improves patient-reported outcomes compared to placebo in subjects with NASH and fibrosis stages 2 or 3. 3. To compare the effects of semaglutide s.c. 2.4 mg versus placebo on cardiovascular disease and cardio-metabolic factors in subjects with NASH and fibrosis stages 2 or 3. 4. To compare the effect of semaglutide s.c. 2.4 mg versus placebo on biomarkers related to fibrosis in subjects with NASH and fibrosis stages 2 or 3.;Primary end point(s): Part 1: 1. Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No) 2. Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No) Part 2: 3. Cirrhosis-free survival (Yes/No);Timepoint(s) of evaluation of this end point: 1.- 2. From randomisation (week 0) to week 72 3. From randomisation (week 0) to week 240 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in body weight 2. Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No) 3. Change in Short Form 36 v2.0 acute (SF-36) Bodily Pain 4. Change in body weight 5. Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No) 6. Change in histology-assessed liver collagen proportionate area 7. Worsening in steatohepatitis (Yes/No) 8. Improvement in histology-assessed ballooning (Yes/No) 9. Improvement in histology-assessed inflammation (Yes/No) 10. Improvement in histology-assessed steatosis (Yes/No) 11. NASH resolution (ballooning of 0, inflammation of 0-1) and =2point NAS reduction with no worsening of fibrosis 12. Progression of liver fibrosis in patients with F2 at baseline (Yes/No) 13. Progression of liver fibrosis 14. Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No) 15. Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No) 16. Changes in liver stiffness values assessed by transient elastography (FibroScan®f) 17. Change in ELF score 18. Change in alanine aminotransferase (ALT) 19. Change in aspartate aminotransferase (AST) 20. Change in CAP values assessed by transient elastography (FibroScan) 21. Change in FAST score 22. Change in Pro-C3 23. Change in inflammation assessed by hsCRP 24. Change in HbA1c 25. Change in triglyceride 26. Change in free fatty acids 27. Change in LDL cholesterol 28. Change in HDL cholesterol 29. Time to first Major Adverse Cardiovascular Event (MACE) (composite endpoint) 30. Major cardio-hepatic event-free survival (Yes/No) 31. Changes in SF-36 Physical Component Summary 32. Changes in SF-36 Mental Component Summary 33. Change in SF-36 Bodily Pain 34. Changes in NASH-CHECK Abdominal Pain;Timepoint(s) of evaluation of this end point: 1. - 3. From randomisation (week 0) to week 72 4. From randomisation (week 0) to week 240 5. - 13. From randomisation (week 0) to week 72 14. - 15. From randomisation | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Denmark, European Union, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Switzerland, Taiwan, Türkiye, United Kingdom, United States
Contacts
Public ContactClinical Transparency (2834)
Novo Nordisk A/S
Outcome results
None listed