Clinical Trials

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

• 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.
• Male or female.
• 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 ≥ 5 years with an alcohol history of a mean of ≥ 50 grams (male)/40 grams (female) pr day for the last year leading up to the time of signing informed consent.
• ELF ≥ 9.8 units.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Documented causes of chronic liver disease other than Alcohol-related liver disease (ALD).
• Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V1) or any known presence of HCV RNA or HBsAg within 2 years of screening (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 NIAAA74).
• Vibration Controlled Transient Elastography LSM ≥ 25 kPa at V2. If participants meet this criterion, rescreening is allowed once.
• Presence or history of gastro-oesophageal varices ≥ grade 2* at V2. For participants with LSM ≥ 20 kPa as well as blood platelets count < 150,000 per 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 insufflation.
• Presence or history of hepatocellular carcinoma at V1
• Any laboratory safety parameters at screening outside the below laboratory ranges, see designated reference range documents for specific values:
  •  ALT > 5x ULN at V1 or AST > 5x ULN at V1.
  • Total bilirubin > 1.5 mg/dL at Vl. Total bilirubin level > 1.5 mg/dL is allowed if conjugated bilirubin is within normal range.
  • Alkaline phosphatase levels > 2 x ULN at Vl.
  • INR of prothrombin time ≥ 1.35 at Vl.
  • MELD score > 12 points at Vl.
  • eGFR < 60 mL/min/1.73 m^2 as defined according to the CKD-EPI creatinine equation (KDIGO 2012) at V1. HbA1c > 80 mmol/mol (9.5%) at Vl. Platelet count< 100,000 per μL of blood at Vl.
• For participants with type 2 diabetes: Uncontrolled and potentially unstable diabetic retinopathy or maculopathy verified by a fundus examination performed within 90 days prior to V1or in the period between V1 and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examinations.
• Treatment with GLP-1 RAs within 90 days prior to Vl.
• Presence of acute pancreatitis within 180 days prior to Vl.
• History or presence of type 1 diabetes at Vl.
• Personal or first-degree relative (s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
• History of seizure disorder (except childhood febrile seizures)
• Active or unstable depression or other active or unstable psychiatric conditionsc which in the investigator's opinion can jeopardise the participant's safety or compliance with the protocol.
• A history of a suicidal attempt within 5 years before screeninge.
• Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at V1 (screening)
• Baseline screening using Montgomery-Asberg Depression Rating Scale (MADRS) at V1 (screening), score corresponding to ≥ 34 (severe depression).
• BMI ≤ 25 kg/m^2.
• Known or suspected hypersensitivity to study intervention(s) or related products.
• Previous participation (i.e., signed informed consent) in this study. If exclusion criteria 5 is met (Vibration Controlled Transient Elastography liver stiffness measurement (LSM) is ≥ 25 kPa), a single rescreening is possible at the investigator's discretion.
• Participation (i.e., signed informed consent) in any other interventional clinical study within 180 days before visit (V1), including any post-treatment follow-up period.
• 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.
• Presence or history of malignant neoplasms other than hepatocellular carcinoma within 5 years prior to V1. Basal and squamous cell skin cancer and any carcinoma in situ are allowed.
• History or presence of chronic pancreatitis at V1.
• Uncontrolled thyroid disease, as assessed by the investigator.
• Any of the following: myocardial infarction, stroke, classification of heart failure NYHA Class IV, hospitalisation for unstable angina pectoris or transient ischaemic attack within 90 days prior to Vl.
• Any participant for whom substantial weight loss might, in the investigator's opinion, jeopardise the safety of the participant.
• Known or suspected drug (including opioids) or chemical substance abuse (excluding alcohol) within 1 year before screening.
• Any condition which might, in the investigator's opinion, jeopardise the safety of the participant or compliance with the protocol.
• Treatment with medications approved for AUD within 90 days prior to Vl (i.e., naltrexone, acamprosate, disulfiram, topiramate, varenicline, or baclofen). Benzodiazepines are allowed for up to 2 weeks as rescue medication for alcohol withdrawal symptoms.
• Sitting blood pressure at screening outside the range of 90-139 mmHg for systolic or 50-89 mmHg for diastolic.
• Pulse outside the range of 50-89 beats/minute at screening.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/15/2024. Questions regarding updates should be directed to the study team contact.