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

Phase 2

Active, not recruiting

• Conditions: Alcohol-related Liver Disease
• Interventions: Drug: NNC0194-0499; Drug: Cagrilintide + semaglutide; Drug: Cagrilintide; Drug: Cagrilintide placebo; Drug: NNC0194-0499 placebo; Drug: Semaglutide placebo (Group B); Drug: Semaglutide placebo (Group A); Drug: Semaglutide

• 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

Study Timeline

• Study First Submitted: 2024-05-07
• Study First Submitted QC: 2024-05-07
• Study First Posted: 2024-05-10
• Study Start: 2024-05-20
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-17
• Last Update Posted: 2025-06-18
• Primary Completion: 2025-11-13
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 270

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 & 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 (85)

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

Scroll for more (75 remaining)