The effect of semaglutide in subjects with non-cirrhotic non-alcoholic steatohepatitis (ESSENCE)

Active, not recruiting

• Conditions: non-cirrhotic non-alcoholic steatohepatitis

• Registration Number: jRCT2031210033
• Lead Sponsor: Novo Nordisk Pharma Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2021-04-12
• Last Update Posted: 2024-08-21

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

1. Histological evidence of NASH (non-alcoholic steatohepatitis) 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 screening visit.
2. Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy.
3. A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 4 with a score of 1 or more in both steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.

Exclusion Criteria

1. Positive HBsAg (hepatitis B surface antigen), positive anti-HIV (human immunodeficiency virus), positive HCV-RNA (Hepatitis C virus RNA) at screening or any known presence of HCV RNA (ribonucleic acid) or HBsAg within 2 years of screening.
2. Documented causes of chronic liver disease other than Non-Alcoholic Fatty Liver Disease NAFLD.
3. Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
4. 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).
5. Treatment with vitamin E (at doses above 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 opinion of the investigator in the period from 90 days prior to the screening visit. 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.
6. Treatment with GLP-1 RAs (glucagon-like peptide-1 receptor agonist) in the period from 90 days prior to the screening visit. 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.
7. 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. 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.

Study & Design

• Study Type: Interventional
• Study Design: parallel assignment

Primary Outcome Measures

Name	Time	Method
Resolution of steatohepatitis and no worsening of liver fibrosis		Resolution of steatohepatitis and no worsening of liver fibrosis
Improvement in liver fibrosis and no worsening of steatohepatitis		Improvement in liver fibrosis and no worsening of steatohepatitis
Time to first liver-related clinical event		Time to first liver-related clinical event (composite endpoint)