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

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 Overview

• Status: Completed
• Conditions: Liver Fibrosis; Hepatic Cirrhosis
• Intervention / Treatment: Drug: AZD2389

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Research Site
  • California
    • Rialto, California, United States, 92377
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30349
      • Research Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Research Site
  • Texas
    • Houston, Texas, United States, 77079
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78215
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A; 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; Doses of AZD2389 or placebo will be administered orally.
Other: Cohort B; 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; Doses of AZD2389 or placebo will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of AZD2389 on plasma FAP activity following oral administration of AZD2389 in participants with CLD and hepatic fibrosis	Inhibition of FAP activity at Days 1, 7, 14, 28, and follow-up (calculated as change and percentage change in FAP activity against baseline) compared to placebo	From Day 1 to Day 35
Maximum Plasma Concentration (Cmax) detected in blood sample	Maximum Plasma Concentration (Cmax)	From Day 1 to Day 35
Time to Maximum Concentration (Tmax) as detected in blood sample	Time to Maximum Concentration (Tmax)	From Day 1 to Day 35
Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClasta) as detected in blood sample	Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClasta)	From Day 1 to Day 35
Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) as detected in blood sample	Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf)	From Day 1 to Day 35
Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau) as detected in blood sample	Area Under the Concentration-time Curve Over a Dosing Interval (AUCtau)	From Day 1 to Day 35
Terminal Half-life (t1/2λz) as detected in blood sample	Terminal Half-life (t1/2λz)	From Day 1 to Day 35
Apparent Volume of Distribution (Vz/F) as detected in blood sample	Apparent Volume of Distribution (Vz/F)	From Day 1 to Day 35
Apparent Clearance (CL/F) as detected in blood sample	Apparent Clearance (CL/F)	From Day 1 to Day 35
Temporal Change Parameter (TCP) as detected in blood sample	Temporal Change Parameter (TCP)	From Day 1 to Day 35
Cmax Accumulation Ratio (Rac Cmax) as detected in blood sample	Cmax Accumulation Ratio (Rac Cmax)	From Day 1 to Day 35
AUC Accumulation Ratio (Rac AUC) as detected in blood sample	AUC Accumulation Ratio (Rac AUC)	From Day 1 to Day 35
Renal Clearance (CLR) as detected in blood sample	Renal Clearance (CLR)	From Day 1 to Day 35
Amount of Drug Excreted in Urine (Ae) as detected in urine sample	Amount of Drug Excreted in Urine (Ae)	From Day 1 to Day 35
Fraction of Drug Excreted in Urine (Fe) as detected in urine sample	Fraction of Drug Excreted in Urine (Fe)	From Day 1 to Day 35

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Actual): July 28, 2025
• Study Completion (Actual): July 28, 2025

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Liver Fibrosis; Hepatic Cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: D7930C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No