Trial · Interventional

CompletedPhase 2Registry data

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

NCTNCT05016882Other idNN9500-4656Other idU1111-1255-5551Other id2020-003566-39

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 2
Enrollment: 698 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 24 countries
United States, Australia, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, India, Italy, Japan, Malaysia, Poland, Portugal, Puerto Rico, Russia, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
Start: 31 Aug 2021
Primary completion: 17 Dec 2024
Completion: 14 Mar 2025
First posted: 23 Aug 2021
Last update posted: 19 Nov 2025
Conditions: Non-alcoholic Steatohepatitis

Timeline

1 trial · 1 completed

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

202120222023202420252026

Ph 2
Research Study on Whether a Combination of 2 Medicines (NNC0194 0499 and Semaglutide) Works in People With Non-alcoholic Steatohepatitis (NASH)
NCT05016882
31 Aug 2021 to 14 Mar 2025

Registry summary

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

This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic steatohepatitis (NASH). NNC0194-0499 is a new medicine which works in the liver. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. It also helps with weight loss and may reduce liver damage, and so prevent future liver complications. It works in a different way to NNC0194 0499. The 2 medicines may work better together than on their own. The study will also look at a combination of semaglutide and another weight-loss medicine called NNC0174-0833, which may be another treatment option for NASH. Each week, participants will get 2 injections. These could be 2 of the 3 medicines OR 1 of the medicines and a placebo OR 2 placebo injections. Which treatment participants get is decided by chance. A placebo is a dummy medicine which looks like the real medicine but doesn't contain any active medicine. The study will last for about 19 months. Participants will have 14 clinic visits and 9 phone calls with the study doctor. Participants will have 1 or 2 liver biopsies (tiny pieces of liver tissue) - one at the start (if participants have not had a biopsy recently) and one at the end of the study treatment. Women: Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Interventions

NNC0194 0499 50 mg/mLDrug
Placebo (NNC0194-0499)Drug
Semaglutide 3 mg/mLDrug
Semaglutide placeboDrug
NNC0174 0833 10 mg/mLDrug
NNC0174 0833 placeboDrug

Arms10

Experimental
NNC0194-0499 7.5 mg + semaglutide 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo comparator
Placebo (NNC0194-0499) 7.5 mg + semaglutide placebo 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Experimental
NNC0194-0499 15 mg + semaglutide 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo comparator
Placebo (NNC0194-0499) 15 mg + semaglutide placebo 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Experimental
NNC0194-0499 30 mg + semaglutide 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Experimental
NNC0194-0499 30 mg + semaglutide placebo 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Active comparator
Placebo (NNC0194-0499) 30 mg + semaglutide 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo comparator
Placebo (NNC0194-0499) 30 mg + semaglutide placebo 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Experimental
NNC0174-0833 2.4 mg + semaglutide 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.
Placebo comparator
Placebo (NNC0174-0833) 2.4 mg + semaglutide placebo 2.4 mg
Each subject will receive two subcutaneous injections once weekly, consisting of two active drugs or one active drug and one placebo or two placebo injections.

Primary outcomes1

Outcomes the sponsor listed as primary.

Improvement in liver fibrosis and no worsening of NASH (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale

Secondary outcomes(20)

Resolution of steatohepatitis and no worsening of liver fibrosis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects Resolution of steatohepatitis is defined as a NAS of 0-1 for inflammation, 0 for ballooning and any value for steatosis according to NASH CRN52. Fibrosis is graded on the NASH CRN (Non-Alcoholic Steatohepatitis Clinical Research Network) fibrosis scale from 0 to 4.
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
Registry description
Count of subjects The 2-point reduction must include at least a 1-point reduction in either lobular inflammation or hepatocellular ballooning.
Change in histology-assessed liver collagen proportionate area
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Resolution of steatohepatitis and improvement in liver fibrosis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects Resolution of steatohepatitis is defined as an NAS score of 0-1 for inflammation, 0 for ballooning and any value for steatosis (according to NASH CRN). Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale
Improvement in liver fibrosis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects Improvement in fibrosis is defined as greater than or equal to 1 grade improvement on the NASH CRN fibrosis scale
Progression of liver fibrosis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects For subjects with fibrosis stage 2 or 3 at baseline
Worsening in steatohepatitis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects Worsening in steatohepatitis is defined as increase in NAS score for ballooning, inflammation or steatosis
Improvement in ballooning (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects
Improvement in inflammation (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects
Improvement in steatosis (Yes/No)
Time frame · From baseline (week 0) to week 52
Registry description
Count of subjects
Change in ALT (alanine aminotransferase)
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in AST (aspartate aminotransferase)
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in inflammation assessed by HsCRP (high sensitivity C-reactive protein)
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in ELF (Enhanced Liver Fibrosis) score
Time frame · From baseline (week 0) to week 52
Registry description
Logarithm
Change in HbA1c. For subjects with type 2 diabetes
Time frame · From baseline (week 0) to week 52
Registry description
%-points (absolute change)
Change in triglycerides
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in free fatty acids
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in LDL (low density lipoprotein) cholesterol
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Change in HDL (high density lipoprotein) cholesterol
Time frame · From baseline (week 0) to week 52
Registry description
Ratio to baseline
Relative change in body weight
Time frame · From baseline (week 0) to week 52
Registry description
Percentage

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.

Completed trials do not always post results.

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

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2026

9 results

Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial.

Loomba et al. 2026The lancet. Gastroenterology & hepatology

PMID 42456707DOI 10.1016/s2468-1253(26)00123-8PUB-42456707

Full text at the publisher9 results

Publisher page See results (9)

Eligibility

Who could join, as posted.

Sex: All
Age: Not stated
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

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