GLP-1 Peptide Atlas, by Delfa

CompletedPhase 2

Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)

Efficacy and Safety Investigation of NNC0194-0499 Co-administered With Semaglutide in Subjects With Non-alcoholic Steatohepatitis: a Dose-ranging, Placebo Controlled Trial

Lead sponsor

Novo Nordisk A/S

Assets

CagriSema / cagrilintide / NNC0194-0499 / Semaglutide

Listed sites

255

Recruiting sites

—

Enrollment

698

actual

Study population

MASH / NAFLD / liver fibrosis

Key I/E criterion

—

Primary endpoint

•Fibrosis ≥1-stage improvement, no MASH worsening

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 IDNCT05016882

Org study IDNN9500-4656

Secondary ID2020-003566-39

Secondary IDU1111-1255-5551World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-08-23actual

Study start2021-08-31actual

Primary completion2024-12-17actual

Study completion2025-03-14actual

Last update posted2025-11-19actual

Assets

Investigational agents

CagriSema / cagrilintide NNC0194-0499 Semaglutide

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosis

Eligibility

Who can enroll

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Aged greater than or equal to 18 years at the time of signing informed consent. In Republic of Korea, subjects must be aged greater than or equal to 19 years. In Japan, subjects must be aged greater than or equal to 20 years. In Singapore, subjects must be aged greater than or equal to 21 years.

•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 Visit 1.

•Histological evidence of fibrosis stage 2, 3 or 4 according to the NASH CRN classification based on a central pathologist evaluation of the baseline liver biopsy.

•Histological non-alcoholic fatty liver disease (NAFLD) activity score (NAS) greater than or equal to 4 for subjects with F2/F3 or greater than or equal to 3 for subjects with F4 based on a central pathologist evaluation of the baseline liver biopsy. All subjects must have a score of 1 or more in steatosis, lobular inflammation and hepatocyte ballooning.

Exclusion criteria

•Documented causes of chronic liver disease other than 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 more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at V2A.

•For subjects with F4, presence or history of gastro-oesophageal varices more than or equal to grade 2 at V3. An oesophagogastroduodenoscopy performed no more than 52 weeks prior to V3 must be available at V3.

•Known or suspected excessive consumption of alcohol (more than 20 g/day for women or more 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 more than or equal to 800 IU/day) or pioglitazone or medications approved for the 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 V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.

•Treatment with GLP-1 RAs within 90 days prior to V2A. Subjects with a historical liver biopsy taken more than 90 days prior to V2A are excluded if they receive treatment with GLP-1 RAs from time of biopsy until 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 V2A. In addition, for subjects with a historical liver biopsy taken more than 90 days prior to V2A, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until V2A.

Endpoints (25)

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

Cardiometabolic biomarkers

Patient-reported / QoL

Weight & body composition

Glycemic / diabetes

Safety / tolerability / PK

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Relative change in body weight

Time frame:From baseline (week 0) to week 52

Body weight, % change

percent change from baseline, improvement

Glycemic / diabetes

1 endpoint

Secondary/protocol endpoint

Change in HbA1c. For subjects with type 2 diabetes

Time frame:From baseline (week 0) to week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

MASH / liver

14 endpoints

Primary/protocol endpoint

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

Time frame:From baseline (week 0) to week 52

Fibrosis ≥1-stage improvement, no MASH worsening

categorical status, improvement

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to week 52

MASH resolution, no fibrosis worsening

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 baseline (week 0) to week 52

categorical status, improvement

Secondary/protocol endpoint

Change in histology-assessed liver collagen proportionate area

Time frame:From baseline (week 0) to week 52

ratio, improvement

Secondary/protocol endpoint

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

Time frame:From baseline (week 0) to week 52

MASH resolution + fibrosis improvement

categorical status, improvement

Secondary/protocol endpoint

Improvement in liver fibrosis (Yes/No)

Time frame:From baseline (week 0) to week 52

Fibrosis ≥1-stage improvement, no MASH worsening

categorical status, improvement

Secondary/protocol endpoint

Progression of liver fibrosis (Yes/No)

Time frame:From baseline (week 0) to week 52

categorical status, improvement

Secondary/protocol endpoint

Worsening in steatohepatitis (Yes/No)

Time frame:From baseline (week 0) to week 52

categorical status, event

Secondary/protocol endpoint

Improvement in ballooning (Yes/No)

Time frame:From baseline (week 0) to week 52

categorical status, improvement

Secondary/protocol endpoint

Improvement in inflammation (Yes/No)

Time frame:From baseline (week 0) to week 52

categorical status, improvement

Secondary/protocol endpoint

Improvement in steatosis (Yes/No)

Time frame:From baseline (week 0) to week 52

categorical status, improvement

Secondary/protocol endpoint

Change in ALT (alanine aminotransferase)

Time frame:From baseline (week 0) to week 52

ALT, change

ratio, improvement

LOINC 1742-6

Secondary/protocol endpoint

Change in AST (aspartate aminotransferase)

Time frame:From baseline (week 0) to week 52

AST, change

ratio, improvement

LOINC 1920-8

Secondary/protocol endpoint

Change in ELF (Enhanced Liver Fibrosis) score

Time frame:From baseline (week 0) to week 52

ELF score, change

change from baseline, improvement

Cardiometabolic biomarkers

5 endpoints

Secondary/protocol endpoint

Change in inflammation assessed by HsCRP (high sensitivity C-reactive protein)

Time frame:From baseline (week 0) to week 52

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in triglycerides

Time frame:From baseline (week 0) to week 52

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in free fatty acids

Time frame:From baseline (week 0) to week 52

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in LDL (low density lipoprotein) cholesterol

Time frame:From baseline (week 0) to week 52

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in HDL (high density lipoprotein) cholesterol

Time frame:From baseline (week 0) to week 52

HDL-C, change

ratio, improvement

LOINC 2085-9

Patient-reported / QoL

3 endpoints

Secondary/protocol endpoint

Change in SF-36 (36-item Short Form Survey) bodily pain

Time frame:From baseline (week 0) to week 52

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

Change in NASH-CHECK (patient-reported outcome measure for non-alcoholic steatohepatitis)pain

Time frame:From baseline (week 0) to week 52

change from baseline, improvement

Secondary/protocol endpoint

Change in PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue score

Time frame:From baseline (week 0) to week 52

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Number of treatment emergent adverse events (TEAEs)

Time frame:From baseline (week 0) to week 59

Treatment-emergent AEs (any)

event count, event

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.