Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease

Effects of NNC0194-0499 Alone and in Combination With Semaglutide, of Semaglutide Alone, and of Cagrilintide Alone and in Combination With Semaglutide on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease

The study will look at the effects of NNC0194-0499, cagrilintide and semaglutide, on liver damage and alcohol use in participants with alcoholic liver disease. Participants will get NNC0194-0499, semaglutide, cagrilintide or ''dummy" medicine in different treatment combinations. Which treatment participants get is decided by chance. The study will last for about 39 weeks.

Study Overview

• Status: Completed
• Conditions: Alcohol-related Liver Disease
• Intervention / Treatment: Drug: NNC0194-0499; Drug: Semaglutide; Drug: Semaglutide placebo (Group A); Drug: NNC0194-0499 placebo; Drug: Cagrilintide + semaglutide; Drug: Cagrilintide; Drug: Semaglutide placebo (Group B); Drug: Cagrilintide placebo

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Momentum Clinical Research Darlinghurst
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital - Storr Liver Centre
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit Box Hill
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne - Gastroenterology Department
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital - Hepatology
• Bulgaria
  • Gorna Oryahovitsa, Bulgaria, 5100
    • MHAT St. Ivan Rilski Gorna Oriahovitsa EOOD
  • Sofia, Bulgaria, 1784
    • Medical Center Synexus Sofia EOOD
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic UMHAT Tokuda EAD, Gastroenterology
  • Sofia, Bulgaria, 1618
    • DCC XX - Sofia EOOD, Gastroenterology
  • Sofia, Bulgaria, 1431
    • UMHAT Aleksandrovska EAD, Clinic of Endocrinology and Metabolic Diseases
  • Sofia, Bulgaria, 1431
    • UMHAT Sveti Ivan Rilski EAD, Gastroenterology
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary Liver Unit-(HMRC)
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Inst Foundation
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences Centre- University Hospital
    • Vaughan, Ontario, Canada, L4L 4Y7
      • TDDA Specialty Research
  • Quebec
    • Terrebonne, Quebec, Canada, J6X 4P7
      • Ctr de méd métab de Lanaudière
• Czechia
  • Liberec, Czechia, 460 01
    • Krajská nemocice Liberec, a.s
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Herlev, Denmark, 2730
    • Herlev Hospital - Gastroenterology and Hepatology, Clinic 3
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital - Gastroenheden
  • Odense C, Denmark, 5000
    • Odense University Hospital - FLASH - Centre for Liver Research
• France
  • Angers, France, 49100
    • Centre Hospitalier Universitaire D'Angers
  • Lille, France, 59000
    • Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez
  • Vénissieux, France, 69200
    • Centre de Recherche Clinique Portes Du Sud
• Germany
  • Homburg, Germany, 66421
    • Universität des Saarlandes - Innere Med. II
  • Leipzig, Germany, 04103
    • Prof. Dr. Schiefke Ingolf, EUGASTRO GmbH
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig - Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie und Pneumologie
  • Lübeck, Germany, 23562
    • Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck
  • Mainz, Germany, 55131
    • Universitätsmedizin der JGU Mainz - Hepatologie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster - Medizinische Klinik B
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg - Zentrum für Innere Medizin (ZIM)
• Greece
  • Goudi/Athens, Greece, 11527
    • "Laiko" General Hospital of Athens
  • Thessaloniki, Greece, 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
  • Attica
    • Athens, Attica, Greece, 12462
      • University Hospital of Athens ATTIKON
• Italy
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino
  • Naples, Italy, 80147
    • Fondazione Evangelica Betania - UO Epatologia
  • Padua, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCS
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • AOU Careggi Firenze
• Japan
  • Bunkyo-ku, Tokyo, Japan, 113-8431
    • Juntendo University Hospital, Gastroenterology
  • Bunkyo-ku, Tokyo, Japan, 113-8431
    • Juntendo University Hospital_Gastroenterology
  • Chiba-shi, Chiba, Japan, 260-0804
    • Akaicho Clinic
  • Gifu, Japan, 503-8502
    • Ogaki Municipal Hospital_Gastroenterology and Hepatology
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic_Internal medicine
  • Kanazawa-shi, Ishikawa, Japan, 920-8530
    • Ishikawa Prefectural Central Hospital_Gastroenterology
  • Kumamoto-shi, Kumamoto, Japan, 862-8655
    • Kumamoto Shinto General Hospital_Liver・Gastroenterology
  • Minato-ku, Tokyo, Japan, 105-8470
    • Toranomon Hospital, Hepatology
  • Nakagamigun, Okinawa, Japan, 901-2492
    • Heartlife Hospital_Liver internal medicine
  • Oita-shi, Oita, Japan, 870-0837
    • Oita Cardiovascular Hospital_Gastroenterology
  • Sapporo-shi, Hokkaido, Japan, 062-8618
    • JCHO Hokkaido Hospital_Digestive Disease Center
  • Suita-shi, Osaka, Japan, 564-0013
    • Saiseikai Suita Hospital, Gastroenterology
  • Tokyo, Japan, 173-8610
    • Nihon University Itabashi Hospital_Division of Gastro.&Hepa.
• Netherlands
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Zkh, Dordwijk
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
  • Tilburg, Netherlands, 5022 GC
    • ETZ Elisabeth
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Poland
  • Krakow, Poland, 31-156
    • "LANDA" Katarzyna Agata Landa
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-605
      • Centrum Medyczne Intercor Sp. z o.o.
    • Torun, Kuyavian-Pomeranian Voivodeship, Poland, 87-100
      • GASTROMED Sp. z o.o.
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-688
      • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
    • Myslowice, Lesser Poland Voivodeship, Poland, 41-400
      • ID Clinic Arkadiusz Pisula
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-507
      • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-540
      • Uniwersytecki Szpital Kliniczny W Bialymstoku
  • West Pomeranian Voivodeship
    • Szczecin, West Pomeranian Voivodeship, Poland, 71-685
      • Sonomed Sp. z o.o.
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic I Provincial
  • España
    • Valladolid, España, Spain, 47003
      • Hospital Clinico Universitario de Valladolid
  • Galicia
    • Pontevedra, Galicia, Spain, 36004
      • Complejo Hospitalario de Pontevedra - Hospital de Montecelo
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health
    • Tucson, Arizona, United States, 85715
      • Del Sol Research Management, LLC
    • Tucson, Arizona, United States, 85712
      • Arizona Liver Center
  • California
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists LLC
    • Hialeah, Florida, United States, 33012
      • Miguel Rebollar PA
    • Jacksonville, Florida, United States, 32224
      • UF Hlth Jacksonville
    • Miami, Florida, United States, 33136
      • Univ of Miami/Schiff Ctr
    • University Park, Florida, United States, 34201
      • Covenant Metabolic Specialists LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Med. Cntr
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic, PA
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center_Cary
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Jubilee Clinical Research, Inc.
  • Ohio
    • Springboro, Ohio, United States, 45066
      • DSI Research,LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC_Center for Liver Care
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Digestive Health Research, TN
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Dallas, Texas, United States, 75203
      • The Liver Institute
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute
    • Houston, Texas, United States, 77030
      • Baylor St. Luke's Medical Center
    • Houston, Texas, United States, 77079
      • Houston Research Institute
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • Amer. Rrsch Corp-TX Liver Inst
    • Sugar Land, Texas, United States, 77479
      • Liver Specialists of Texas
    • Waco, Texas, United States, 76710
      • Velocity Clinical Res, Waco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Age 18 years or above, and at the legal drinking age according to local requirements at the time of signing the informed consent.
• Patient-reported history of alcohol overuse for greater than or equal to 5 years with an alcohol history of a mean of greater than or equal to 50 grams (male)/40 grams (female) pr day for the last year leading up to the time of signing informed consent.
• Enhanced Liver Fibrosis (ELF) greater than or equal to 9.0 units.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention(s) or related products (incl. excipients).
• Previous participation (i.e., signed informed consent) in this study. If exclusion criteria 7 is met (Vibration Controlled Transient Elastography liver stiffness measurement (LSM) is greater than or equal to 25 Kilopascal (kPa)), a single rescreening is possible at the investigator's discretion.
• Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
• Positive hepatitis B surface antigen (HBsAg), positive human immunodeficiency virus-1 (HIV-1) or HIV-2 antibody (Ab), positive hepatitis C virus (HCV) ribonucleic acid (RNA) at screening (V1) or any known presence of HCV RNA or HBsAg within 2 years of screening visit 1 (V1).
• Presence or history of ascites more than grade 1, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or liver transplantation at screening (V1).
• Alcohol hepatitis at randomisation (as defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA)).
• Vibration Controlled Transient Elastography liver stiffness measurement (LSM) greater than or equal to 25 kPa at visit 2 (V2). If participants meet this criterion, rescreening is allowed once.
• Presence or history of gastro-oesophageal varices greater than or equal to grade 2* at V2. For participants with LSM greater than or equal to 20 kPa as well as blood platelets count less than 150,000 per microliter (μL) of blood an oesophagogastroduodenoscopy performed no more than 52 weeks prior to V2 must be available at V2. *Grade 2: varices projecting by one-third of the luminal diameter that cannot be compressed with air insufflation4.
• Body mass index (BMI) less than or equal to 25 Kilogram Per Square Meter (kg/m^2).
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method with low user-dependency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNC0194-0499 + semaglutide; Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.	Drug: NNC0194-0499; Administered subcutaneously.; Drug: Semaglutide; Administered subcutaneously.
Experimental: NNC0194-0499 + semaglutide placebo; Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.	Drug: NNC0194-0499; Administered subcutaneously.; Drug: Semaglutide placebo (Group A); Administered subcutaneously.
Experimental: NNC0194-0499 placebo + semaglutide; Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.	Drug: Semaglutide; Administered subcutaneously.; Drug: NNC0194-0499 placebo; Administered subcutaneously.
Placebo Comparator: NNC0194-0499 placebo + semaglutide placebo; Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.	Drug: Semaglutide placebo (Group A); Administered subcutaneously.; Drug: NNC0194-0499 placebo; Administered subcutaneously.
Experimental: CagriSema; Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide.	Drug: Cagrilintide + semaglutide; Administered subcutaneously.
Experimental: Cagrilintide + semaglutide placebo; Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.	Drug: Cagrilintide; Administered subcutaneously.; Drug: Semaglutide placebo (Group B); Administered subcutaneously.
Placebo Comparator: Cagrilintide placebo + semaglutide placebo; Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.	Drug: Semaglutide placebo (Group B); Administered subcutaneously.; Drug: Cagrilintide placebo; Administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Enhanced Liver Fibrosis (ELF)	Measured as logarithm score	From week 0 to week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pro-peptide of Collagen 3 (Pro-C3)	Measured as ratio to baseline	From week 0 to week 28
Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE)	Measured as ratio to baseline	From week 0 to week 28
Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP)	Measured as decibel milliwatts (dB/m)	From week 0 to week 28
Change in Alanine Aminotransferase (ALT)	Measured as ratio to baseline	From week 0 to week 28
Change in Aspartate Aminotransferase (AST)	Measured as ratio to baseline	From week 0 to week 28
Number of treatment emergent adverse events	Measured as count of events	From week 0 to week 35
Change in Phosphatidylethanol (PEth)	Measured as ratio to baseline	From week -4 to week 28
Change in alcohol amount measured by timeline followback (TLFB)	Measured as grams per day	From week -4 to week 28
Change in total cholesterol	Measured as ratio to baseline	From week 0 to week 28

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Actual): November 21, 2025
• Study Completion (Actual): January 12, 2026

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide; cagrilintide
• Other Study ID Numbers: NN9500-7730; U1111-1295-6713 (Other Identifier: World Health Organization (WHO)); 2023-508170-28 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No