Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease
- Conditions
- Alcohol-related Liver Disease
- Interventions
- Drug: Cagrilintide placeboDrug: NNC0194-0499 placebo
- Registration Number
- NCT06409130
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 270
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NNC0194-0499 + semaglutide NNC0194-0499 Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide. NNC0194-0499 + semaglutide placebo NNC0194-0499 Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo. NNC0194-0499 placebo + semaglutide NNC0194-0499 placebo Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide. NNC0194-0499 placebo + semaglutide placebo NNC0194-0499 placebo Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo. CagriSema Cagrilintide + semaglutide Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide. Cagrilintide + semaglutide placebo Cagrilintide Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo. Cagrilintide + semaglutide placebo Semaglutide placebo (Group B) Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo. Cagrilintide placebo + semaglutide placebo Cagrilintide placebo Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo. Cagrilintide placebo + semaglutide placebo Semaglutide placebo (Group B) Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo. NNC0194-0499 placebo + semaglutide placebo Semaglutide placebo (Group A) Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo. NNC0194-0499 + semaglutide placebo Semaglutide placebo (Group A) Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo. NNC0194-0499 + semaglutide Semaglutide Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide. NNC0194-0499 placebo + semaglutide Semaglutide Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.
- Primary Outcome Measures
Name Time Method Change in Enhanced Liver Fibrosis (ELF) From week 0 to week 28 Measured as logarithm score
- Secondary Outcome Measures
Name Time Method Change in Pro-peptide of Collagen 3 (Pro-C3) From week 0 to week 28 Measured as ratio to baseline
Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE) From week 0 to week 28 Measured as ratio to baseline
Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP) From week 0 to week 28 Measured as decibel milliwatts (dB/m)
Change in Alanine Aminotransferase (ALT) From week 0 to week 28 Measured as ratio to baseline
Change in Aspartate Aminotransferase (AST) From week 0 to week 28 Measured as ratio to baseline
Number of treatment emergent adverse events From week 0 to week 35 Measured as count of events
Change in Phosphatidylethanol (PEth) From week -4 to week 28 Measured as ratio to baseline
Change in alcohol amount measured by timeline followback (TLFB) From week -4 to week 28 Measured as grams per day
Change in total cholesterol From week 0 to week 28 Measured as ratio to baseline
Trial Locations
- Locations (89)
"Acibadem City Clinic UMHAT Tokuda"
🇧🇬Sofia, Bulgaria
The Institute for Liver Health
🇺🇸Chandler, Arizona, United States
Arizona Liver Center
🇺🇸Tucson, Arizona, United States
Del Sol Research Management, LLC
🇺🇸Tucson, Arizona, United States
OM Research LLC
🇺🇸Lancaster, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Covenant Metabolic Specialists LLC
🇺🇸University Park, Florida, United States
Miguel Rebollar PA
🇺🇸Hialeah, Florida, United States
UF Hlth Jacksonville
🇺🇸Jacksonville, Florida, United States
Univ of Miami/Schiff Ctr
🇺🇸Miami, Florida, United States
Rush University Med. Cntr
🇺🇸Chicago, Illinois, United States
Kansas Medical Clinic, PA
🇺🇸Topeka, Kansas, United States
Boston Medical Center_Cary
🇺🇸Boston, Massachusetts, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Jubilee Clinical Research, Inc.
🇺🇸Las Vegas, Nevada, United States
DSI Research,LLC
🇺🇸Springboro, Ohio, United States
University of Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Digestive Health Research, TN
🇺🇸Hermitage, Tennessee, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
The Liver Institute
🇺🇸Dallas, Texas, United States
South Texas Research Institute
🇺🇸Edinburg, Texas, United States
Baylor St. Luke's Medical Center
🇺🇸Houston, Texas, United States
Houston Research Institute
🇺🇸Houston, Texas, United States
Amer. Rrsch Corp-TX Liver Inst
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
Velocity Clinical Res, Waco
🇺🇸Waco, Texas, United States
Momentum Clinical Research Darlinghurst
🇦🇺Darlinghurst, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Eastern Clinical Research Unit Box Hill
🇦🇺Box Hill, Victoria, Australia
St Vincent's Hospital (Melbourne)
🇦🇺Fitzroy, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Fiona Stanley Hospital - Hepatology
🇦🇺Murdoch, Western Australia, Australia
Multiprofile Hospital For Active Treatment St. Ivan Rilski Gorna Oriahovitsa EOOD
🇧🇬Gorna Oryahovitsa, Bulgaria
UMHAT "Sv. Ivan Rilski", Clinic of Gastroenterology
🇧🇬Sofia, Bulgaria
"DCC XX - Sofia" EOOD
🇧🇬Sofia, Bulgaria
Medical Center Synexus Sofia
🇧🇬Sofia, Bulgaria
University of Calgary Liver Unit-(HMRC)
🇨🇦Calgary, Alberta, Canada
GI Research Inst Foundation
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Centre- University Hospital
🇨🇦London, Ontario, Canada
TDDA Specialty Research
🇨🇦Vaughan, Ontario, Canada
Ctr de Med Metab de Lanaudiere
🇨🇦Terrebonne, Quebec, Canada
Krajská nemocice Liberec, a.s
🇨🇿Liberec, Czechia
Vseobecna Fakultni nemocnice v Praze
🇨🇿Prague 2, Czechia
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Herlev Hospital
🇩🇰Herlev, Denmark
Hvidovre Hospital - Gastroenheden
🇩🇰Hvidovre, Denmark
Odense University Hospital
🇩🇰Odense C, Denmark
Centre Hospitalier Universitaire D'Angers-1
🇫🇷Angers, France
Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez
🇫🇷Lille, France
Centre de Recherche Clinique Portes Du Sud
🇫🇷Venissieux, France
Universitätsmedizin der Johannes-Gutenberg-Universität Mainz - Hepatologie
🇩🇪Mainz, Germany
Universitätsklinikum des Saarlandes - Klinik für Innere Medizin II
🇩🇪Homburg, Germany
University Hospital of Athens ATTIKON
🇬🇷Athens, Attica, Greece
Universitätsklinikum Leipzig - Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie und Pneumologie
🇩🇪Leipzig, Germany
Universitätsklinikum Würzburg, Zentrum für Innere Medizin (ZIM)
🇩🇪Würzburg, Germany
"Laiko" General Hospital of Athens
🇬🇷Goudi/Athens, Greece
'Ippokrateio' General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
AOU Careggi Firenze
🇮🇹Firenze, Toscana, Italy
IRCCS Azienda Ospedaliero Universitaria San Martino - IST
🇮🇹Genova, Italy
Ospedale Evangelico Betania
🇮🇹Naples, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Juntendo University Hospital, Gastroenterology
🇯🇵Bunkyo-ku, Tokyo, Japan
Akaicho Clinic
🇯🇵Chiba-shi, Chiba, Japan
Ogaki Municipal Hospital_Gastroenterology and Hepatology
🇯🇵Gifu, Japan
Naka Kinen Clinic
🇯🇵Ibaraki, Japan
Ishikawa Prefectural Central Hospital_Gastroenterology
🇯🇵Kanazawa-shi, Ishikawa, Japan
Kumamoto Shinto General Hospital
🇯🇵Kumamoto-shi, Kumamoto, Japan
Toranomon Hospital, Hepatology
🇯🇵Minato-ku, Tokyo, Japan
Heartlife Hospital
🇯🇵Nakagamigun, Okinawa, Japan
Oita Cardiovascular Hospital
🇯🇵Oita-shi, Oita, Japan
Japan Community Health care Organization Hokkaido Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Saiseikai Suita Hospital, Gastroenterology
🇯🇵Suita-shi, Osaka, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Japan
Albert Schweitzer Ziekenhuis locatie Dordwijk
🇳🇱Dordrecht, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
ETZ Elisabeth
🇳🇱Tilburg, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Centrum Medyczne Intercor Sp. z o.o.
🇵🇱Bydgoszcz, Kujawsko-Pomorskie, Poland
Gastromed Sp. z o.o.
🇵🇱Toruń, Kujawsko-pomorskie, Poland
ID Clinic Arkadiusz Pisula
🇵🇱Mysłowice, Malopolskie, Poland
PANSTWOWY INSTYTUT MEDYCZNY MSWiA
🇵🇱Warszawa, Mazowieckie, Poland
Sonomed Sp. Z O.O.
🇵🇱Szczecin, Zachodniopomorskie, Poland
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Cataluña, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, España, Spain
Complejo Hospitalario de Pontevedra - Hospital de Montecelo
🇪🇸Pontevedra, Galicia, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain