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
Notable Trends in Laboratory Assessments (Haematology, Coagulation, Clinical Chemistry, Fibrinolysis, and Urinalysis)	The number of participants with notable trends in laboratory assessments (haematology, coagulation, clinical chemistry, fibrinolysis, and urinalysis) is presented. Notable trends were assessed based on evaluation of mean values over time, individual participant values, and clinically important abnormalities, including values outside predefined criteria.	From screening up to and including Day 35
Clinically Relevant Trends in Vital Signs (Blood Pressure, Pulse Rate, Oxygen Saturation, Body Temperature, and Respiration Rate), and 12-lead Electrocardiogram (ECG)	The number of participants with clinically relevant trends in vital signs (blood pressure, pulse rate, oxygen saturation, body temperature, and respiration rate), and12-lead ECGs is presented. Clinically relevant trends were assessed based on trends or group changes over time, changes in individual participants over time, and individual clinically important abnormalities.	From Screening up to and including Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Cmax	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Cmax= Maximum Concentration	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Tmax	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. tmax = Time to Maximum Concentration	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: t1/2 Lambda z	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. t1/2 lambda z= Apparent Terminal Half-life	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. AUClast= Area Under the Concentration-time Curve to the Last Measurable Concentration AUCinf = Area Under the Concentration-time Curve Extrapolated to Infinity AUCtau = Area Under the Concentration-time Curve Over a Dosing Interval AUCtau presented as AUC(0-24h) in the table. In line with standard PK analysis methodologies, AUCinf was estimated only for Day 1. AUClast and AUCtau were estimated for both Day 1 and Day 28.	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Lambda z	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. lambda z = Terminal elimination rate constant	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Vz/F	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Vz/F = Apparent Volume of Distribution	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: CL/F and CLR	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. CL/F = Apparent Clearance CLR = Renal Clearance	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: TCP AUC	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. TCP is calculated as the ratio of steady-state AUCtau (AUC0-24h) to first-dose AUCinf TCP = Temporal Change Parameter AUC = Area Under the Concentration-time Curve	Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Rac AUC and Rac Cmax	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Rac AUC = AUC Accumulation Ratio; ratio of steady state AUCtau (AUC0-24h)/First Dose AUCtau (AUC0-24h) Rac Cmax = Cmax Accumulation Ratio; ratio of steady state Cmax/First Dose Cmax	Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Ae (0-24)	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Ae (0-24) = Cumulative Amount of Drug Excreted Unchanged in Urine	Day 1 and Day 28
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Fe (0-24)	The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Fe = Fraction of Dose Excreted Unchanged into Urine	Day 1 and Day 28
Inhibition of FAP Activity Calculated as Percentage Change in FAP Activity Against Baseline Compared to Placebo.	Effect of AZD2389 on plasma FAP activity following oral administration of AZD2389 in participants with chronic Liver Disease and hepatic fibrosis was evaluated and presented as percentage change from baseline in FAP activity. Percentage change when comparing post-treatment visits to baseline for each group, calculated as (Geometric LS mean - 1) *100. FAP=Fibroblast Activating Protein	Day 28

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• d7930c00002_Redacted CSR synopsis
• d7930c00002_Redacted_SAP
• d7930c00002_Redacted_CSP

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): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Liver Fibrosis; Hepatic Cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; 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