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

Novo Nordisk

Status and phase: Enrolling; Phase 2

Conditions: Alcohol-related Liver Disease

Treatments: Drug: Cagrilintide; Drug: NNC0194-0499 placebo; Drug: Semaglutide placebo (Group B); Drug: Semaglutide placebo (Group A); Drug: Cagrilintide placebo; Drug: NNC0194-0499; Drug: Cagrilintide + semaglutide; Drug: Semaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06409130

U1111-1295-6713 (Other Identifier)

NN9500-7730

2023-508170-28 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 (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 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

240 participants in 7 patient groups, including a placebo group

NNC0194-0499 + semaglutide

Experimental group

Description:

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide.

Treatment:

Drug: Semaglutide

Drug: NNC0194-0499

NNC0194-0499 + semaglutide placebo

Experimental group

Description:

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 in combination with semaglutide placebo.

Treatment:

Drug: NNC0194-0499

Drug: Semaglutide placebo (Group A)

NNC0194-0499 placebo + semaglutide

Experimental group

Description:

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide.

Treatment:

Drug: Semaglutide

Drug: NNC0194-0499 placebo

NNC0194-0499 placebo + semaglutide placebo

Placebo Comparator group

Description:

Group A: Participants will receive subcutaneous (s.c.) injections of NNC0194-0499 placebo in combination with semaglutide placebo.

Treatment:

Drug: Semaglutide placebo (Group A)

Drug: NNC0194-0499 placebo

CagriSema

Experimental group

Description:

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide.

Treatment:

Drug: Cagrilintide + semaglutide

Cagrilintide + semaglutide placebo

Experimental group

Description:

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide in combination with semaglutide placebo.

Treatment:

Drug: Semaglutide placebo (Group B)

Drug: Cagrilintide

Cagrilintide placebo + semaglutide placebo

Placebo Comparator group

Description:

Group B: Participants will receive subcutaneous (s.c.) injection of cagrilintide placebo in combination with semaglutide placebo.

Treatment:

Drug: Cagrilintide placebo

Drug: Semaglutide placebo (Group B)