Study of AZD2389 Safety, Tolerability, and Pharmacodynamics in Adults With Steatotic Liver Disease and Advanced Fibrosis (BRAVO)

A Phase IIa, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AZD2389 in Adult Participants With Steatotic Liver Disease and Advanced Fibrosis (BRAVO)

The purpose of this study is to evaluate the safety, tolerability, and pharmacodynamic effects of AZD2389 in adult participants with steatotic liver disease (SLD) and advanced fibrosis.

Study Overview

• Status: Recruiting
• Conditions: Liver Fibrosis; Hepatic Cirrhosis
• Intervention / Treatment: Other: Placebo; Drug: AZD2389

Detailed Description

Study details include:

• The study duration will be approximately 32 weeks, including screening duration of 4 weeks, the treatment duration of up to 24 weeks, and follow-up period of 4 weeks.
• The visit frequency will be approximately every 4 weeks except from Visit 2 to Visit 4, which is every 2 weeks.

Disclosure Statement:

This is a parallel group treatment study that is blinded to the participants and investigators.

Number of Participants:

Approximately 230 participants with SLD and advanced fibrosis will be screened such that approximately 104 participants will be randomised. Approximately 52 participants will be randomised to receive AZD2389 and approximately 52 participants will receive placebo.

Note: 'Screened' means a participant's, or their legally authorised representative's, agreement to participate in a clinical study following completion of the informed consent process.

Study Arms and Duration:

Arm A will include 52 participants with SLD and advanced fibrosis who will receive oral AZD2389 for 24 weeks. Arm B will include 52 participants with SLD and advanced fibrosis who will receive oral placebo for 24 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Not yet recruiting
      • Research Site
  • Florida
    • Jupiter, Florida, United States, 33458
      • Not yet recruiting
      • Research Site
    • Miami, Florida, United States, 33122
      • Not yet recruiting
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Not yet recruiting
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Not yet recruiting
      • Research Site
    • St Louis, Missouri, United States, 63123
      • Not yet recruiting
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Not yet recruiting
      • Research Site
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Recruiting
      • Research Site
    • Raleigh, North Carolina, United States, 27607
      • Not yet recruiting
      • Research Site
  • Ohio
    • Westlake, Ohio, United States, 44145
      • Not yet recruiting
      • Research Site
  • Oklahoma
    • Yukon, Oklahoma, United States, 73099
      • Not yet recruiting
      • Research Site
  • Tennessee
    • Clarksville, Tennessee, United States, 37040
      • Not yet recruiting
      • Research Site
  • Texas
    • Austin, Texas, United States, 78757
      • Not yet recruiting
      • Research Site
    • Denison, Texas, United States, 75020
      • Not yet recruiting
      • Research Site
    • Georgetown, Texas, United States, 78626
      • Not yet recruiting
      • Research Site
    • Houston, Texas, United States, 77079
      • Not yet recruiting
      • Research Site
    • Houston, Texas, United States, 77004
      • Not yet recruiting
      • Research Site
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • Research Site
    • San Antonio, Texas, United States, 78222
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Males/females aged 18 or over
• A diagnosis of SLD with advanced fibrosis
• No significant change in weight over the last 6 months
• Contraceptive us by participants or participants partners
• Capable of giving informed consent
• Judged by the investigator to be suitable for study

Key Exclusion Criteria:

• Portal hypertension (LSM >25 kPa or 20-25 kPa with platelets <150×10⁹/L), decompensated liver disease, Child-Pugh >A6, MELD >12, other chronic liver diseases, prior/planned liver transplant, or malignant liver tumors.
• Positive viral infections, including HIV or hepatitis B, or hepatitis C unless HCV RNA-negative ≥12 weeks after treatment.
• Alcohol intake above protocol thresholds, or positive screen for drugs of abuse.
• Significant metabolic, cardiovascular, or GI disorders, including T1DM or insulin-treated T2DM, uncontrolled hypertension, recent major cardiac/cerebrovascular events, severe heart failure, serious arrhythmias, significant pancreatic disease, or major GI surgery.
• History of psychosis, bipolar disorder, recent major depression, or suicide attempt/ideation within 1 year.
• Bleeding risk or wound-healing concerns, including coagulation disorders, major bleeding history, active wounds or recent major surgery, or severe dermatologic immune conditions.
• Prohibited medications or hypersensitivities, including moderate/strong CYP3A4 or BCRP/OAT3 inhibitors/inducers, anticoagulants/antiplatelets (except aspirin ≤81 mg/day), or hypersensitivity to DPP4 inhibitors.
• Other protocol-defined exclusions, including significant abnormal labs (e.g., worsening ALT/AST), recent participation in another IMP study, or investigator judgment of unsuitability.

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
Experimental: Arm A; Doses of AZD2389 to be administered orally.	Drug: AZD2389; potent, selective, first-in-class, small molecule oral inhibitor of FAP and is being developed for the treatment of CLDs with advanced hepatic fibrosis including cirrhosis.; Other Names: Active IMP
Placebo Comparator: Arm B; Doses of placebo to be administered orally.	Other: Placebo; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in Enhanced Liver Fibrosis (ELF) score from baseline to week 24	To evaluate the effects of AZD2389 versus placebo on improvement in ELF score. Lowered ELF scores would suggest better outcome. Note: ELF is not bounded, i.e. there are no minimum and maximum values	24 weeks
Reported quantity and severity of adverse events (AEs)	To assess the safety and tolerability of AZD2389 in participants with SLD and advanced fibrosis	Up to and including Day 197
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 197
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 197
Number of participants with abnormal laboratory results detected in urine samples	Urinalysis - Paper chromatography	Up to and including Day 197
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 197
Number of participants with observed changes in Sp02 oxygen values against baseline measurement	Sp02 oxygen saturations measured by percentage	Up to and including Day 197
Number of participants with observed changes in body temperature against baseline value	Body temperature measured in degrees Celsius	Up to and including Day 197
Number of participants with observed changes in respiratory rate against baseline value	Respiratory rate measured in respirations per minute	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Hematology - Platelets (x10^9/L)	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Coagulation - INR	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Clinical Chemistry - ALT (U/L)	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Fibrinolysis - D-dimer (ng/mL fibrinogen-equivalent units)	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Clinical Chemistry - AST (U/L)	Up to and including Day 197
Number of participants with abnormal laboratory test results detected in blood samples	Clinical Chemistry - ALP (U/L)	Up to and including Day 197

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24	To assess the effects of AZD2389 versus placebo on improvement in ProC3	24 weeks
Absolute change in Liver Stiffness Measurement (LSM) from baseline to week 24	To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE)	24 weeks
Absolute change in Controlled Attenuation Parameter (CAP) from baseline to week 24	To assess the effects of AZD2389 versus placebo on improvement in CAP	24 weeks
Percentage change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24	To assess the effects of AZD2389 versus placebo on improvement in ProC3	24 weeks
Percentage change in Liver Stiffness Measurement (LSM) from baseline to week 24	To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE)	24 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2026
• Primary Completion (Estimated): July 7, 2027
• Study Completion (Estimated): July 7, 2027

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 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: D7930C00008

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