Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH)

Phase 3Active Not RecruitingNCT04822181

Novo Nordisk A/S1,205 enrolled

Overview

Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. Participants will either get semaglutide or a dummy medicine - which treatment participants get is decided by chance. Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week. The study will last for about 5 years. Participants will have up to 21 clinic visits and 9 phone calls with the clinical staff during the study. Some of the clinic visits may be spread over more than one day. Participants with other chronic liver diseases cannot take part in this study. Women cannot take part in the study if they are pregnant, breast-feeding or plan to become pregnant during the study period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,205

Conditions

Non-alcoholic Steatohepatitis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy. * A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 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. 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 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.

Locations (558)

North AL Health Res, LLC

Huntsville, Alabama, United States

The Institute for Liver Health

Chandler, Arizona, United States

Inst-Liver Hlth dba AZ Liver H

Peoria, Arizona, United States

Inst. Liver H II dba AZ Liver H

Tucson, Arizona, United States

Del Sol Research Management, LLC

Tucson, Arizona, United States

Outcomes

Primary Outcomes

Part 1: Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Part 1: Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Part 2: Cirrhosis-free survival (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 240

Secondary Outcomes

Change in body weight

Percentage

Time frame: From randomisation (week 0) to week 72

Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Change in SF-36 (Short Form 36) Bodily Pain

Score points

Time frame: From randomisation (week 0) to week 72

Change in body weight

Percentage

Time frame: From randomisation (week 0) to week 240

Improvement in steatohepatitis with at least a 2-point reduction in NAS and no worsening of fibrosis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Change in histology-assessed liver collagen proportionate area

Ratio to baseline

Time frame: From randomisation (week 0) to week 72

Worsening in steatohepatitis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Improvement in histology-assessed ballooning (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Improvement in histology-assessed inflammation (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Improvement in histology-assessed steatosis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

NASH resolution (ballooning of 0, inflammation of 0-1) and above or equal to 2point NAS reduction with no worsening of fibrosis

Count of subject

Time frame: From randomisation (week 0) to week 72

Progression of liver fibrosis in patients with F2 at baseline (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 72

Progression of liver fibrosis

Count of subject

Time frame: From randomisation (week 0) to week 72

Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 240

Improvement in liver fibrosis and no worsening of steatohepatitis (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 240

Absence of histological evidence of NASH (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 240

Changes in liver stiffness values assessed by transient elastography (FibroScan®)

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in ELF (Enhanced Liver Fibrosis) score

Logarithm

Time frame: From randomisation (week 0) to week 72 and week 240

Change in ALT (alanine aminotransferase)

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in AST (aspartate aminotransferase)

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in CAP (Controlled Attenuation Parameter) values assessed by transient elastography (FibroScan)

Absolute change

Time frame: From randomisation (week 0) to week 72 and week 240

Change in FAST (FibroScan-AST) score

Probability (absolute change)

Time frame: From randomisation (week 0) to week 72 and week 240

Change in Pro-C3 (pro-peptide of type III collagen)

Logarithm

Time frame: From randomisation (week 0) to week 72 and week 240

Change in inflammation assessed by hsCRP (High Sensitive C-Reactive Protein)

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in HbA1c (glycated haemoglobin)

Percentage-points (absolute change)

Time frame: From randomisation (week 0) to week 72 and week 240

Change in triglyceride

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in free fatty acids

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in LDL (low-density lipoprotein) cholesterol

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Change in HDL (High density lipoprotein ) cholesterol

Ratio to baseline

Time frame: From randomisation (week 0) to week 72 and week 240

Time to first MACE(Major Adverse Cardiovascular event ) (composite endpoint)

Days

Time frame: From randomisation (week 0) to week 240

Major cardio-hepatic event-free survival (Yes/No)

Count of subject

Time frame: From randomisation (week 0) to week 240

Changes in SF-36 (Short Form 36 v2.0 acute ) Physical Component Summary

Score points

Time frame: From randomisation (week 0) to week 72 and week 240

Changes in SF-36 Mental Component Summary

Score points

Time frame: From randomisation (week 0) to week 72 and week 240

Change in SF-36 Bodily Pain

Score points

Time frame: From randomisation (week 0) to week 240

Changes in NASH-CHECK Abdominal Pain

Score points

Time frame: From randomisation (week 0) to week 72 and week 240