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

Alcohol-related Liver Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06409130
• Other study ID #: NN9500-7730
• Secondary ID: U1111-1295-67132
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2024
• Est. completion date: September 6, 2025

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: September 6, 2025
• Est. primary completion date: June 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 9.8 units.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention(s) or related products.

• 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 anti-human immunodeficiency virus (anti-HIV), 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.

Related Conditions & MeSH terms

• Alcohol-related Liver Disease
• Liver Diseases

Intervention

Drug:
• NNC0194-0499
Administered subcutaneously.
• Semaglutide
Administered subcutaneously.
• NNC0194-0499 placebo
Administered subcutaneously.
• Semaglutide placebo (Group A)
Administered subcutaneously.
• Cagrilintide + semaglutide
Administered subcutaneously.
• Cagrilintide
Administered subcutaneously.
• Cagrilintide placebo
Administered subcutaneously.
• Semaglutide placebo (Group B)
Administered subcutaneously.

Locations

Country	Name	City	State
Australia	Eastern Clinical Research Unit Box Hill	Box Hill	Victoria
Australia	Holdsworth House Clinical Research	Darlinghurst	New South Wales
Australia	St Vincent's Hospital (Melbourne)	Fitzroy	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Fiona Stanley Hospital - Hepatology	Murdoch	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Bulgaria	Multiprofile Hospital For Active Treatment St. Ivan Rilski Gorna Oriahovitsa EOOD	Gorna Oryahovitsa
Bulgaria	"Acibadem City Clinic MHAT Tokuda"	Sofia
Bulgaria	"DCC XX - Sofia" EOOD	Sofia
Bulgaria	Medical Center Synexus Sofia	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", Clinic of Gastroenterology	Sofia
Bulgaria	UMHAT Aleksandrovska	Sofia
Canada	University of Calgary Liver Unit-(HMRC)	Calgary	Alberta
Canada	London Health Sciences Centre- University Hospital	London	Ontario
Canada	Ctr de Med Metab de Lanaudiere	Terrebonne	Quebec
Canada	GI Research Institute	Vancouver	British Columbia
Canada	TDDA Specialty Research	Vaughan	Ontario
Czechia	Krajská nemocice Liberec, a.s	Liberec
Czechia	Vseobecna Fakultni nemocnice v Praze	Prague 2
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Herlev Hospital	Herlev
Denmark	Hvidovre Hospital	Hvidovre
Denmark	Odense University Hospital	Odense C
France	Centre Hospitalier Universitaire D'Angers-1	Angers
France	Centre Hospitalier Universitaire de Lille-Hopital Claude Huriez	Lille
France	Groupe Hospitalier Mutualiste Des Portes Du Sud	Venissieux
Germany	Universitätsklinikum des Saarlandes - Klinik für Innere Medizin II	Homburg
Germany	Prof. Dr. Schiefke Ingolf, EUGASTRO GmbH	Leipzig
Germany	Universitätsklinikum Leipzig, Klinik und Poliklinik	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Universitätsmedizin der Johannes-Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Münster - Medizinische Klinik B	Münster
Germany	Universitätsklinikum Würzburg, ZIM	Würzburg
Greece	"Laiko" General Hospital of Athens	Goudi/Athens
Greece	University Hospital of Athens ATTIKON	Haidari-Athens	Attica
Greece	'Ippokrateio' General Hospital of Thessaloniki	Thessaloniki
Greece	'Ippokrateio' General Hospital of Thessaloniki	Thessaloniki
Italy	AOU Careggi Firenze	Firenze
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
Japan	Ogaki Municipal Hospital_Gastroenterology and Hepatology	Gifu
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	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
Netherlands	Albert Schweitzer Ziekenhuis locatie Dordwijk	Dordrecht
Netherlands	Erasmus MC	Rotterdam
Netherlands	ETZ Elisabeth	Tilburg
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	Centrum Medyczne Intercor Sp. z o.o.	Bydgoszcz	Kujawsko-Pomorskie
Poland	"LANDA" Katarzyna Agata Landa	Kraków
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital w Krakowie	Kraków	Malopolskie
Poland	ID Clinic Arkadiusz Pisula	Myslowice	Malopolskie
Poland	Sonomed Sp. Z O.O.	Szczecin	Zachodniopomorskie
Poland	Gastromed Sp. z o.o.	Torun	Kujawsko-pomorskie
Poland	PANSTWOWY INSTYTUT MEDYCZNY MSWiA	Warszawa	Mazowieckie
Spain	Hospital Clinic i Provincial	Barcelona	Cataluña
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Complejo Hospitalario de Pontevedra - Hospital de Montecelo	Pontevedra	Galicia
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Valladolid	Valladolid	España
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Boston Medical Center_Cary	Boston	Massachusetts
United States	The Institute for Liver Health	Chandler	Arizona
United States	Rush University Med. Cntr	Chicago	Illinois
United States	The Liver Institute	Dallas	Texas
United States	Digestive Health Research, TN	Hermitage	Tennessee
United States	Miguel Rebollar PA	Hialeah	Florida
United States	Houston Research Institute	Houston	Texas
United States	Liver Specialists of Texas	Houston	Texas
United States	UF Hepatology Jacksonville	Jacksonville	Florida
United States	OM Research LLC	Lancaster	California
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Univ of Miami/Schiff Ctr	Miami	Florida
United States	California Liver Research Institute	Pasadena	California
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	UPMC_Center for Liver Care	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Amer. Rrsch Corp-TX Liver Inst	San Antonio	Texas
United States	Covenant Metabolic Specialists LLC	Sarasota	Florida
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Kansas Medical Clinic, PA	Topeka	Kansas
United States	Arizona Liver Center	Tucson	Arizona
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Velocity Clinical Res, Waco	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Netherlands,  Poland,  Spain, 

Outcome

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