DelfaGLP-1 Atlas

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ESSENCE

Active not recruitingPhase 3

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

The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

556

Recruiting sites

—

Enrollment

1,205

actual

Study population

MASH / NAFLD / liver fibrosis

Key I/E criterion

—

Primary endpoints

•MASH resolution, no fibrosis worsening•Fibrosis ≥1-stage improvement, no MASH worsening•Progression to cirrhosis

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04822181
Org study IDNN9931-4553
Secondary ID2019-004594-44European Medicines Agency (EudraCT)
Secondary IDjRCT2031210033JAPIC
Secondary IDU1111-1244-3678World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-03-30actual
Study start2021-04-01actual
Last update posted2026-04-17actual
Primary completion2029-04-25estimated
Study completion2029-04-25estimated

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosis

Eligibility

Who can enroll

Minimum age18 Years
SexAll
Healthy volunteersNot accepted

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.

Endpoints (38)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

MASH / liver
23
Cardiometabolic biomarkers
5
Patient-reported / QoL
5
Weight & body composition
2
Cardiovascular outcomes
1
Glycemic / diabetes
1
Other (unclassified)
1

Cardiovascular outcomes

1 endpoint
Secondary/protocol endpoint/low confidence

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

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

Expanded / custom MACE composite

time to event, event

Weight & body composition

2 endpoints
Secondary/protocol endpoint

Change in body weight

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

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in body weight

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

Body weight, % change

percent change from baseline, improvement

Glycemic / diabetes

1 endpoint
Secondary/protocol endpoint

Change in HbA1c (glycated haemoglobin)

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

HbA1c, change

change from baseline, improvement

LOINC 4548-4

MASH / liver

23 endpoints
Primary/protocol endpoint

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

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

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Primary/protocol endpoint

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

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

Fibrosis ≥1-stage improvement, no MASH worsening

categorical status, improvement

Primary/protocol endpoint

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

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

Progression to cirrhosis

categorical status, improvement

Secondary/protocol endpoint

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

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

MASH resolution + fibrosis improvement

categorical status, improvement

Secondary/protocol endpoint

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

categorical status, improvement

Secondary/protocol endpoint

Change in histology-assessed liver collagen proportionate area

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

ratio, improvement

Secondary/protocol endpoint

Worsening in steatohepatitis (Yes/No)

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

categorical status, event

Secondary/protocol endpoint

Improvement in histology-assessed ballooning (Yes/No)

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

categorical status, improvement

Secondary/protocol endpoint

Improvement in histology-assessed inflammation (Yes/No)

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

categorical status, improvement

Secondary/protocol endpoint

Improvement in histology-assessed steatosis (Yes/No)

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

categorical status, improvement

Secondary/protocol endpoint

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

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Secondary/protocol endpoint

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

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

categorical status, improvement

Secondary/protocol endpoint

Progression of liver fibrosis

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

Fibrosis, no progression

event count, event

Secondary/protocol endpoint

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

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

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Secondary/protocol endpoint

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

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

Fibrosis ≥1-stage improvement, no MASH worsening

categorical status, improvement

Secondary/protocol endpoint

Absence of histological evidence of NASH (Yes/No)

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

categorical status, improvement

SNOMED 442685003

Secondary/protocol endpoint

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

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

Liver stiffness (VCTE), change

ratio, improvement

Secondary/protocol endpoint

Change in ELF (Enhanced Liver Fibrosis) score

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

ELF score, change

change from baseline, improvement

Secondary/protocol endpoint

Change in ALT (alanine aminotransferase)

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

ALT, change

ratio, improvement

LOINC 1742-6

Secondary/protocol endpoint

Change in AST (aspartate aminotransferase)

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

AST, change

ratio, improvement

LOINC 1920-8

Secondary/protocol endpoint

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

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

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in FAST (FibroScan-AST) score

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

change from baseline, improvement

Secondary/protocol endpoint/low confidence

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

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

change from baseline, improvement

Cardiometabolic biomarkers

5 endpoints
Secondary/protocol endpoint

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

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in triglyceride

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

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in free fatty acids

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

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in LDL (low-density lipoprotein) cholesterol

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

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in HDL (High density lipoprotein ) cholesterol

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

HDL-C, change

ratio, improvement

LOINC 2085-9

Patient-reported / QoL

5 endpoints
Secondary/protocol endpoint

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

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

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

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

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

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

Changes in SF-36 Mental Component Summary

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

SF-36 mental

change from baseline, improvement

Secondary/protocol endpoint

Change in SF-36 Bodily Pain

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

change from baseline, improvement

Secondary/protocol endpoint

Changes in NASH-CHECK Abdominal Pain

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

change from baseline, improvement

Other (unclassified)

1 endpoint
Secondary/protocol endpoint/low confidence

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

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

categorical status, event

Publications (3)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.