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

NCT06750276 | Completed Phase 2 FDA Drug

• 1 other identifier: D7930C00002
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 9

Brief Summary

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

Conditions

Liver Fibrosis; Hepatic Cirrhosis

Keywords

Liver Fibrosis; Hepatic Cirrhosis

Outcome Measures

Primary Outcomes (11)

• Reported quantity and severity of adverse events (AEs) following oral administration of AZD2389

  Reporting frequency and severity of AEs based on qualifying symptoms, signs, abnormalities in measured values, or other diagnoses as identified by investigator

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with observed changes in blood pressure against baseline mmHg value

  Assess blood pressure level (with systolic and diastolic pressure) in mmHg

  Up to and including Day 35 (from pre-screening to follow-up visit)

• Number of participants with observed changes in heart rate (BPM) against baseline value

  Pulse rate measured in beats per minute (BPM)

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with observed changes in Sp02 oxygen values against baseline measurement

  Sp02 oxygen saturations measured by percentage

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with observed changes in body temperature against baseline value

  Body temperature measured in degrees Celsius

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with observed changes in respiratory rate against baseline value

  Respiratory rate measured in respirations per minute

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with identified abnormalities in results of 12-lead safety electrocardiograms (ECG)

  12-lead safety ECG (PR interval, QRS complex, ST interval, T wave)

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with changes in physical baseline values identified during physical examinations

  Physical examinations will include assessment of general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, musculoskeletal (including spine and extremities) and neurological symptoms (examination of the participants' feet to observe skin integrity, circulation, and presence of any neuropathy).

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with abnormal laboratory test results detected in blood samples

  Hematology - Platelets (x10\^9/L) Clinical Chemistry - ALT (U/L), AST (U/L), ALP (U/L) Coagulation - INR Fibrinolysis - D-dimer (ng/mL fibrinogen-equivalent units)

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with abnormal laboratory results detected in urine samples

  Urinalysis - Paper chromatography

  Up to and including day 35 (from pre-screening to follow-up visit)

• Number of participants with visible changes (against baseline observations) to the condition of abdominal organs as identified by FibroScan imaging

  FibroScan (VCTE) ultrasound imaging will measure a participant's level of LSM (liver stiffness), CAP (amount of fat in the liver), and/or SSM (spleen stiffness).

  Up to and including Day 35 (from pre-screening to follow-up visit)

Secondary Outcomes (15)

• To evaluate the effect of AZD2389 on plasma FAP activity following oral administration of AZD2389 in participants with CLD and hepatic fibrosis

  From Day 1 to Day 35

• Maximum Plasma Concentration (Cmax) detected in blood sample

  From Day 1 to Day 35

• Time to Maximum Concentration (Tmax) as detected in blood sample

  From Day 1 to Day 35

• Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClasta) as detected in blood sample

  From Day 1 to Day 35

• Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) as detected in blood sample

  From Day 1 to Day 35

Study Arms (2)

Cohort A

OTHER

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.

Drug: AZD2389

Cohort B

OTHER

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.

Drug: AZD2389

Interventions

AZD2389 DRUG

Doses of AZD2389 or placebo will be administered orally.

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (9)

Research Site

Chandler, Arizona, 85224, United States

Location

Research Site

Rialto, California, 92377, United States

Location

Research Site

Atlanta, Georgia, 30349, United States

Location

Research Site

Morehead City, North Carolina, 28557, United States

Location

Research Site

Houston, Texas, 77079, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

San Juan, 00927, Puerto Rico

Location

Research Site

Cambridge, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a single-blind, randomized, placebo-controlled study with up to 2 study intervention cohorts that are participant and investigator-blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The total duration of study participation for each participant in Cohorts A and B will be approximately 63 days (9 weeks) and will include an up to 28-day screening period, a 28-day treatment period, and a follow-up visit seven days following completion of treatment. Assessments will be conducted as described in the SoA.

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 27, 2024
• Study Start: December 6, 2024
• Primary Completion: July 28, 2025
• Study Completion: July 28, 2025
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (7); PR (1); GB (1)