Non-alcoholic steatohepatitis MedDRA version: 22.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: NNC0174-0833 A 10 mg/mL
Product Code: [N/A]
Pharmaceutical Form: Solution for injection in cartridge
Current Sponsor code: N/A
Concentration unit: mg/ml milligram(s)/millilitre
Concentra
Sponsors
NOVO NORDISK. S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Aged greater than or equal to 18 years at the time of signing informed consent. - Histological evidence of non-alcoholic steatohepatitis (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 visit 1. - Histological evidence of fibrosis stage 2, 3 or 4 according to the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) classification based on a central pathologist evaluation of the baseline liver biopsy. - Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning. 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 504 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 168
Exclusion criteria
Exclusion criteria: - Documented causes of chronic liver disease other than NAFLD. - Positive Hepatitis B surface antigen (HBsAg), positive anti-human immunodeficiency virus (HIV), positive hepatitis C virus ribonucleic acid (HCV RNA) at screening visit 2A (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A). - Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A. - Presence or history of gastro-oesophageal varices greater than or equal to grade 2 at V2A. For subjects with F4, an oesophagogastroduodenoscopy performed no more than 52 weeks prior to V2A must be available at V2A. - 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 the treatment of NASH which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A. - Treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RAs) within 90 days prior to V2A. Subjects with a historical liver biopsy taken more than 90 days prior to V2A are excluded if they receive treatment with GLP-1 RAs from time of biopsy until 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 V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the effect of NNC0194-0499 30 mg once weekly in combination with semaglutide 2.4 mg once weekly versus placebo once weekly on fibrosis in subjects with NASH and fibrosis stage 2-4 (F2- F4).;Secondary Objective: In subjects with NASH and F2-F4: • To investigate the dose-response relationship of NNC0194-0499 (7.5 mg, 15 mg and 30 mg) once weekly in combination with semaglutide 2.4 mg once weekly on liver histology and tolerability. • To investigate the safety and tolerability of NNC0194-0499 30 mg once weekly alone, NC0194-0499 7.5 mg, 15 mg and 30 mg once weekly in combination with semaglutide 2.4 mg once weekly and NNC0174-0833 2.4 mg once weekly in combination with semaglutide 2.4 mg once weekly.;Primary end point(s): Improvement in liver fibrosis and no worsening of NASH (Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale. No worsening of NASH is defined as no increase from baseline in NAS score for ballooning, inflammation or steatosis.) (Yes/No).;Timepoint(s) of evaluation of this end point: From baseline (week 0) to week 52. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No) 2. Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No) 3. Change in histology-assessed liver collagen proportionate area 4. Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No) 5. Improvement in liver fibrosis (Yes/No) 6. Progression of liver fibrosis (Yes/No) 7. Worsening in steatohepatitis (Yes/No) 8. Improvement in ballooning (Yes/No) 9. Improvement in inflammation (Yes/No) 10. Improvement in steatosis (Yes/No) 11. Change in ALT (alanine aminotransferase) 12. Change in AST (aspartate aminotransferase) 13. Change in inflammation assessed by HsCRP (high sensitivity Creactive protein) 14. Change in (Enhanced Liver Fibrosis) ELF score 15. Change in (glycated haemoglobin) HbA1c 16. Change in triglycerides 17. Change in free fatty acids 18. Change in low density lipoprotein (LDL) cholesterol 19. Change in high density lipoprotein (HDL) cholesterol 20. Relative change in body weight 21. Change in (36-item Short Form Survey) SF-36 bodily pain 22. Change in Patient reported outcome measure for non-alcoholic steatohepatitis (NASH-CHECK) pain 23. Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score 24. Number of treatment emergent adverse events (TEAEs);Timepoint(s) of evaluation of this end point: 1.-23. From baseline (week 0) to week 52 24. From baseline (week 0) to week 59 | — |
Countries
Australia, Canada, European Union, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Russian Federation, Singapore, United Kingdom, United States
Contacts
Public ContactClinical Transparency (1452)
Novo Nordisk A/S
Outcome results
None listed