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Trial · Interventional

Active, not recruitingPhase 3Registry data

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

Short name ESSENCE

NCTNCT04822181 (opens ClinicalTrials.gov in a new tab)Other idNN9931-4553Other idU1111-1244-3678Other id2019-004594-44Other idjRCT2031210033

Overview

Status
Active, not recruiting
Phase
Phase 3
Enrollment
1,205 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
30 countries

United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, Denmark, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Romania, Russia, Serbia

Start
1 Apr 2021
Primary completion
25 Apr 2029 (estimated)
Completion
25 Apr 2029 (estimated)
First posted
30 Mar 2021
Last update posted
13 Oct 2026
Conditions
Non-alcoholic Steatohepatitis

Timeline

1 trial · 1 ongoing

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20222024202620282030
  1. Ph 3

    ESSENCE

    NCT04822181

    1 Apr 2021 to est. 25 Apr 2029

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SemaglutideDrug
  • PlaceboDrug

Arms2

  • Experimental

    Semaglutide OW (once weekly )

    Semaglutide administrated subcutaneously once weekly

  • Placebo comparator

    Placebo

    Placebo administrated subcutaneously once weekly

Primary outcomes3

Outcomes the sponsor listed as primary.

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

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

Secondary outcomes(20)
  1. Change in body weight

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

    Registry description

    Percentage

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

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

    Registry description

    Count of subject

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

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

    Registry description

    Score points

  4. Change in body weight

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

    Registry description

    Percentage

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

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

    Registry description

    Count of subject

  6. Change in histology-assessed liver collagen proportionate area

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

    Registry description

    Ratio to baseline

  7. Worsening in steatohepatitis (Yes/No)

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

    Registry description

    Count of subject

  8. Improvement in histology-assessed ballooning (Yes/No)

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

    Registry description

    Count of subject

  9. Improvement in histology-assessed inflammation (Yes/No)

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

    Registry description

    Count of subject

  10. Improvement in histology-assessed steatosis (Yes/No)

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

  13. Progression of liver fibrosis

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

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

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

    Registry description

    Count of subject

  16. Absence of histological evidence of NASH (Yes/No)

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

    Registry description

    Count of subject

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

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

    Registry description

    Ratio to baseline

  18. Change in ELF (Enhanced Liver Fibrosis) score

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

    Registry description

    Logarithm

  19. Change in ALT (alanine aminotransferase)

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

    Registry description

    Ratio to baseline

  20. Change in AST (aspartate aminotransferase)

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

    Registry description

    Ratio to baseline

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2025

6 results

Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

Sanyal et al. 2025The New England journal of medicinecited by 778

PMID 40305708DOI 10.1056/nejmoa2413258PUB-40305708

Full text at the publisher6 results

Indexing hint: Clinical trial · 2024

Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial.

Newsome et al. 2024Alimentary pharmacology & therapeuticscited by 105

PMID 39412509PMC11599791DOI 10.1111/apt.18331PUB-39412509

CC BY
Download PDF

More studies

1 study on this page

PubMed tag: none · 2026

Semaglutide in Japanese participants with metabolic dysfunction-associated steatohepatitis: a subgroup analysis of the ESSENCE trial.

Nakajima et al. 2026Journal of gastroenterology

PMID 42663669DOI 10.1007/s00535-026-02507-0PUB-42663669

Full text at the publisher
Publisher page

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedJensen EL, Israelsen M, Krag A. Transforming steatotic liver disease management: The emerging role of GLP-1 receptor agonists. Hepatol Commun. 2024 Oct 10;8(11):e0561. doi: 10.1097/HC9.0000000000000561. eCollection 2024 Nov 1. PMID 39392766
  • DerivedRowe IA, Allen AM. Hepatic steatosis provides the terroir that promotes the development of cardiovascular risk factors and disease. Hepatology. 2023 Jun 1;77(6):1843-1845. doi: 10.1097/HEP.0000000000000327. Epub 2023 Feb 6. No abstract available. PMID 36738088

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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