This study is looking at alcohol-related liver disease, which is damage to the liver caused by long-term heavy alcohol use. The liver is an organ that helps clean the blood and perform many important body functions, and excessive alcohol consumption over time can cause scarring and inflammation of the liver tissue. The study will test several medications given as injections under the skin. These include zalfermin (also known as NNC0194-0499), cagrilintide, and semaglutide. Some participants will receive these medications alone, while others will receive combinations of cagrilintide with semaglutide or zalfermin with semaglutide. Some participants will receive placebo. The purpose of the study is to find out if these medications, used alone or in combination, can reduce liver damage and improve liver function in people with alcohol-related liver disease, and also to see if they affect alcohol use.

During the study, participants will receive their assigned treatment for up to 28 weeks. The study will measure changes in the liver by looking at specific markers in the blood that show liver scarring and damage, such as the Enhanced Liver Fibrosis score and other substances that indicate how much scar tissue is forming in the liver. The study will also use a special ultrasound device that measures liver stiffness and fat content by sending gentle vibrations through the liver. Blood tests will check liver enzymes, which are proteins released when liver cells are damaged, and cholesterol levels. To understand effects on alcohol use, the study will measure a substance in the blood called phosphatidylethanol that indicates recent alcohol consumption, and participants will report their alcohol intake over time. The study will also carefully monitor any side effects that occur during treatment.

Participants in this study must be adults who have a history of drinking significant amounts of alcohol regularly for at least five years and who have evidence of liver damage based on blood test results. The study will compare how well the different medications work by measuring changes in liver health markers and alcohol use from the beginning to the end of the treatment period.