A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis.

A Phase 2a, Randomised, Single-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics and Explore the Pharmacodynamic Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis

The purpose of this study is to measure the safety, tolerability, and the way the body absorbs, distributes, and metabolises AZD2389 as compared to placebo in participants with liver fibrosis and compensated cirrhosis. The study will also examine how the drug acts on the body

Study details include:

The study duration will be up to 63 days (9 weeks).

• 1 or 2 screening visits (up to 28 days before treatment)
• 28 days of treatment including 5 clinic visits
• Week 1: 24-hour in-clinic stay (Day 1)
• Week 2: Outpatient clinic visit (Day 7)
• Week 3: Outpatient clinic visit (Day 14)
• Week 4: Telephone visit (Day 21)
• Week 5: 24 to 48-hour in-clinic stay (Day 28)
• Week 6: Follow-up visit (Day 35) Disclosure Statement: The study consists of two cohorts, each with a parallel-group design and two arms, with participants blinded to treatment allocation.

Number of Participants:

The study will randomise approximately 36 participants in total. Cohort A: Approximately 75 participants with presumed MASH/NASH with fibrosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo. Cohort B: Approximately 75 participants with SLD with advanced fibrosis including compensated cirrhosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo

Key inclusions:

• Males/females aged ≥ 18 years
• Indications: Presumed MASH (cohort A) or other steatotic liver disease (cohort B) with fibrosis
• No significant change in weight over the last 6 months
• Barrier contraceptives use by males
• Capable of informed consent
• Judged to be suitable for study by investigator

Key exclusions:

• A condition that could put the participant at risk, influence the participant's ability to participate in the trial, interfere with evaluation of the study intervention or affect the interpretation of the results
• Other causes of liver disease which are not the principal inclusion criteria for each cohort
• Significant elevations in liver blood tests or platelets <140 x10^9/L
• Decompensated liver disease, hepatobiliary cancer or listing for liver transplantation
• Bleeding disorders or major bleeding risk
• HIV infection or hepatitis B infection
• Clinically significant cardiovascular (e.g. severe ischaemic heart disease, severe heart failure or cardiac dysrhythmia) or cerebrovascular disease within the past 3 months
• Stage 2 hypertension
• eGFR <60ml/min/1.73m2
• Clinically significant gastrointestinal disease which can affect the interpretation of pharmacokinetic, safety, and tolerability data
• Skin disorders or ongoing wound healing
• Psychiatric disorders which may negatively affect participation in the trial.
• Females of childbearing potential