Non-alcoholic steatohepatitis Compensated liver cirrhosis MedDRA version: 20.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 20.0 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 10019805 -
Conditions
Interventions
Trade Name: Ozempic®
Product Name: Semaglutide B 3.0 mg/ml PDS290
Pharmaceutical Form: Solution for injection
INN or Proposed INN: semaglutide
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion 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 above14 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 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 57 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of semaglutide subcutaneous (s.c.) 2.4 mg once-weekly on liver fibrosis compared with placebo in subjects with NASH and compensated fibrosis stage 4; Secondary Objective: 1. To investigate the effect of semaglutide s.c. 2.4 mg once-weekly on NASH compared with placebo in subjects with NASH and compensated fibrosis stage 4 2, To evaluate the safety and tolerability of semaglutide s.c. 2.4 mg once-weekly compared with placebo in subjects with NASH and compensated fibrosis stage 4 ;Primary end point(s): Relative change in liver stiffness measured by MRE;Timepoint(s) of evaluation of this end point: From baseline (week 0) to visit 12 (week 48) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Relative change in liver fat content (%) measured by MRI-PDFF 2. At least one stage of liver fibrosis improvement with no worsening of NASH (yes/no) (worsening defined as an increase of at least one stage of either lobular inflammation, hepatocyte ballooning or steatosis according to the NASH CRN criteria) 3. NASH resolution (yes/no) (defined by the NASH CRN as lobular inflammation 0 – 1 and ballooning 0) 4. Change in Stage of fibrosis according to the NASH CRN fibrosis score 5. Change in NAFLD activity score (NAS) according to the NASH CRN criteria 6. Number of treatment emergent adverse events ; Timepoint(s) of evaluation of this end point: All secondary endpoints: From baseline (week 0) to visit 12 (week 48) | — |
Countries
European Union, France, Spain, United Kingdom, United States
Contacts
Public ContactClinical Disclosure (1452)
Novo Nordisk A/S
Outcome results
None listed