Hepatic Cirrhosis, Liver Fibrosis
Conditions
Keywords
Liver Fibrosis, Hepatic Cirrhosis
Brief 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.
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.
Interventions
DRUGAZD2389
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.
OTHERPlacebo
Oral administration
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a parallel group treatment study that is blinded to the participants and investigators.
Intervention model description
This is a Phase IIa, randomised, double-blind, placebo-controlled, multicentre study to assess the safety, tolerability and PD effects of AZD2389 in participants with SLD and advanced fibrosis. Randomisation will be stratified by, type 2 diabetes mellitus (T2DM), and alcohol use. The purpose of this study is to evaluate the safety, tolerability, and PD of AZD2389 in adult participants with SLD and advanced fibrosis. 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24 | 24 weeks | To assess the effects of AZD2389 versus placebo on improvement in ProC3 |
| Absolute change in Liver Stiffness Measurement (LSM) from baseline to week 24 | 24 weeks | To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE) |
| Absolute change in Controlled Attenuation Parameter (CAP) from baseline to week 24 | 24 weeks | To assess the effects of AZD2389 versus placebo on improvement in CAP |
| Percentage change in Procollagen Type III N-terminal Propeptide (ProC3) from baseline to week 24 | 24 weeks | To assess the effects of AZD2389 versus placebo on improvement in ProC3 |
| Percentage change in Liver Stiffness Measurement (LSM) from baseline to week 24 | 24 weeks | To assess the effects of AZD2389 versus placebo on improvement in LSM measured by Vibration-controlled transient elastography (VCTE) |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed