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.
Placebo: Oral administration
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Absolute change in Enhanced Liver Fibrosis (ELF) score from baseline to week 24 — 24 weeks 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
Reported quantity and severity of adverse events (AEs) — Up to and including Day 197 To assess the safety and tolerability of AZD2389 in participants with SLD and advanced fibrosis
Number of participants with observed changes in blood pressure against baseline mmHg value — Up to and including Day 197 Assess blood pressure level (with systolic and diastolic pressure) in mmHg
Number of participants with identified abnormalities in results of 12-lead safety electrocardiograms (ECG) — Up to and including Day 197 12-lead safety ECG (PR interval, QRS complex, ST interval, T wave)
Number of participants with abnormal laboratory results detected in urine samples — Up to and including Day 197 Urinalysis - Paper chromatography
Number of participants with observed changes in heart rate (BPM) against baseline value — Up to and including Day 197 Pulse rate measured in beats per minute (BPM)
Number of participants with observed changes in Sp02 oxygen values against baseline measurement — Up to and including Day 197 Sp02 oxygen saturations measured by percentage
Number of participants with observed changes in body temperature against baseline value — Up to and including Day 197 Body temperature measured in degrees Celsius
Number of participants with observed changes in respiratory rate against baseline value — Up to and including Day 197 Respiratory rate measured in respirations per minute
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Hematology - Platelets (x10\^9/L)
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Coagulation - INR
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Clinical Chemistry - ALT (U/L)
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Fibrinolysis - D-dimer (ng/mL fibrinogen-equivalent units)
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Clinical Chemistry - AST (U/L)
Number of participants with abnormal laboratory test results detected in blood samples — Up to and including Day 197 Clinical Chemistry - ALP (U/L)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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