Clinical trial NCT06409130: Effects of NNC0194-0499, Cagrilintide, and Semaglutide Alone or in Combinations on Liver Damage and Alcohol Use in People With Alcohol-related Liver Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alcohol-related Liver Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-05-10
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Enhanced Liver Fibrosis (ELF)
timeFrame: From week 0 to week 28
Secondary outcomes:
measure: Change in Pro-peptide of Collagen 3 (Pro-C3)
timeFrame: From week 0 to week 28
measure: Change in liver stiffness assessed by Vibration Controlled Transient Elastography (VCTE)
timeFrame: From week 0 to week 28
measure: Change in liver steatosis assessed by Controlled Attenuated Parameter (CAP)
timeFrame: From week 0 to week 28
measure: Change in Alanine Aminotransferase (ALT)
timeFrame: From week 0 to week 28
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: From week 0 to week 28
measure: Number of treatment emergent adverse events
timeFrame: From week 0 to week 35
measure: Change in Phosphatidylethanol (PEth)
timeFrame: From week -4 to week 28
measure: Change in alcohol amount measured by timeline followback (TLFB)
timeFrame: From week -4 to week 28
measure: Change in total cholesterol
timeFrame: From week 0 to week 28
Other outcomes:
Locations:
city: Chandler
country: United States
facility: The Institute for Liver Health
state: Arizona
city: Tucson
country: United States
facility: Arizona Liver Center
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Lancaster
country: United States
facility: OM Research LLC
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists LLC
state: Florida
city: Hialeah
country: United States
facility: Miguel Rebollar PA
state: Florida
city: Jacksonville
country: United States
facility: UF Hlth Jacksonville
state: Florida
city: Miami
country: United States
facility: Univ of Miami/Schiff Ctr
state: Florida
city: University Park
country: United States
facility: Covenant Metabolic Specialists LLC
state: Florida
city: Chicago
country: United States
facility: Rush University Med. Cntr
state: Illinois
city: Topeka
country: United States
facility: Kansas Medical Clinic, PA
state: Kansas
city: Boston
country: United States
facility: Boston Medical Center_Cary
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: Jubilee Clinical Research, Inc.
state: Nevada
city: Springboro
country: United States
facility: DSI Research,LLC
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Hermitage
country: United States
facility: Digestive Health Research, TN
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: The Liver Institute
state: Texas
city: Edinburg
country: United States
facility: South Texas Research Institute
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Research Institute
state: Texas
city: San Antonio
country: United States
facility: Amer. Rrsch Corp-TX Liver Inst
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Waco
country: United States
facility: Velocity Clinical Res, Waco
state: Texas
city: Darlinghurst
country: Australia
facility: Momentum Clinical Research Darlinghurst
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit Box Hill
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital (Melbourne)
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital - Hepatology
state: Western Australia
city: Gorna Oryahovitsa
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment St. Ivan Rilski Gorna Oriahovitsa EOOD
city: Sofia
country: Bulgaria
facility: "Acibadem City Clinic UMHAT Tokuda"
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", Clinic of Gastroenterology
city: Sofia
country: Bulgaria
facility: "DCC XX - Sofia" EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Synexus Sofia
city: Calgary
country: Canada
facility: University of Calgary Liver Unit-(HMRC)
state: Alberta
city: Vancouver
country: Canada
facility: GI Research Inst Foundation
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre- University Hospital
state: Ontario
city: Vaughan
country: Canada
facility: TDDA Specialty Research
state: Ontario
city: Terrebonne
country: Canada
facility: Ctr de Med Metab de Lanaudiere
state: Quebec
city: Liberec
country: Czechia
facility: Krajská nemocice Liberec, a.s
city: Prague 2
country: Czechia
facility: Vseobecna Fakultni nemocnice v Praze
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital - Gastroenheden
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Angers
country: France
facility: Centre Hospitalier Universitaire D'Angers-1
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez
city: Venissieux
country: France
facility: Centre de Recherche Clinique Portes Du Sud
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes - Klinik für Innere Medizin II
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie und Pneumologie
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes-Gutenberg-Universität Mainz - Hepatologie
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Zentrum für Innere Medizin (ZIM)
city: Athens
country: Greece
facility: University Hospital of Athens ATTIKON
state: Attica
city: Goudi/Athens
country: Greece
facility: "Laiko" General Hospital of Athens
city: Thessaloniki
country: Greece
facility: 'Ippokrateio' General Hospital of Thessaloniki
city: Firenze
country: Italy
facility: AOU Careggi Firenze
state: Toscana
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliero Universitaria San Martino - IST
city: Naples
country: Italy
facility: Ospedale Evangelico Betania
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Bunkyo-ku, Tokyo
country: Japan
facility: Juntendo University Hospital, Gastroenterology
city: Chiba-shi, Chiba
country: Japan
facility: Akaicho Clinic
city: Gifu
country: Japan
facility: Ogaki Municipal Hospital_Gastroenterology and Hepatology
city: Ibaraki
country: Japan
facility: Naka Kinen Clinic
city: Kanazawa-shi, Ishikawa
country: Japan
facility: Ishikawa Prefectural Central Hospital_Gastroenterology
city: Kumamoto-shi, Kumamoto
country: Japan
facility: Kumamoto Shinto General Hospital
city: Minato-ku, Tokyo
country: Japan
facility: Toranomon Hospital, Hepatology
city: Nakagamigun, Okinawa
country: Japan
facility: Heartlife Hospital
city: Oita-shi, Oita
country: Japan
facility: Oita Cardiovascular Hospital
city: Sapporo-shi, Hokkaido
country: Japan
facility: Japan Community Health care Organization Hokkaido Hospital
city: Suita-shi, Osaka
country: Japan
facility: Saiseikai Suita Hospital, Gastroenterology
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Intercor Sp. z o.o.
state: Kujawsko-Pomorskie
city: Toruń
country: Poland
facility: Gastromed Sp. z o.o.
state: Kujawsko-pomorskie
city: Mysłowice
country: Poland
facility: ID Clinic Arkadiusz Pisula
state: Malopolskie
city: Warszawa
country: Poland
facility: PANSTWOWY INSTYTUT MEDYCZNY MSWiA
state: Mazowieckie
city: Szczecin
country: Poland
facility: Sonomed Sp. Z O.O.
state: Zachodniopomorskie
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
state: Cataluña
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
state: España
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra - Hospital de Montecelo
state: Galicia
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: