Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Active IMP
AZD2389 · 6 trials · 5 indications
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
To assess the safety and tolerability of AZD2389 in participants with SLD and advanced fibrosis
Assess blood pressure level (with systolic and diastolic pressure) in mmHg
12-lead safety ECG (PR interval, QRS complex, ST interval, T wave)
Urinalysis - Paper chromatography
Pulse rate measured in beats per minute (BPM)
Sp02 oxygen saturations measured by percentage
Body temperature measured in degrees Celsius
Respiratory rate measured in respirations per minute
Hematology - Platelets (x10\^9/L)
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.
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.
To examine target FAP occupancy in the liver by AZD2389 as measured with \[68Ga\]Ga-FAPI-46 PET.
To assess the effect of quinidine on the PK of AZD2389.
To assess the effect of quinidine on the PK of AZD2389.
To assess the effect of quinidine on the PK of AZD2389.
To assess the PK parameter RCmax for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter RAUCinf for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter RAUClast for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.
To assess the PK parameter ratio of AUC0-24 for caffeine in combination with AZD2389 compared to caffeine alone.
maximum observed plasma concentration
area under the concentration-time curve from zero to infinity
area under the concentration-time curve from zero to the last measurable concentration
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Doses of AZD2389 to be administered orally. |
| Arm B | PLACEBO_COMPARATOR | Doses of placebo to be administered orally. |
| Cohort A | OTHER | 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 | OTHER | 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. |
| Part A | OTHER | In Part A, eligible participants (screening Visit 1) will return to the trial site for pre-assessments, confirmation of eligibility criteria, blood sampling for FAP concentration analysis (at the trial site), and the first PET examination (screening Visit 2). The participants will perform the PET examination at the PET Centre using the radioligand \[68Ga\]Ga-FAPI-46. Depending on the results of the initial PET examination, participants of Part A may be invited to continue the trial in Part B. In such a case they will participate in a total of 3 PET examinations, not exceeding predefined radiation exposure limits. If they do not participate further, they will complete the trial with a follow-up visit (Visit 3, telephone call) 7 days (±2 days) after the PET examination. |
| Part B1 | EXPERIMENTAL | In Part B1, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part B2 | EXPERIMENTAL | In Part B2, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part B3 | EXPERIMENTAL | In Part B3, eligible participants who completed the first PET scan at the screening visit and/or Part A will return to the trial site for blood sampling for FAP concentration analysis and the second PET examination on Day 1 (Visit 3) using the radioligand \[68Ga\]Ga-FAPI-46. At Visit 4, on Day 7 (±2 days), participants will receive a single oral dose of AZD2389. After AZD2389 administration, the third PET examination will be performed at the PET Centre followed by blood sampling for PK analysis and FAP activity, after which the participants will return to the trial site for further follow-up and safety monitoring. The participants will then be discharged from the trial site. Two follow up visits will occur after administration of AZD2389. Visit 5 (7 days \[±2 days\]) and Visit 6 (30 days\[+7 days\]) will monitor for safety and follow-up of AEs. |
| Part C | EXPERIMENTAL | In Part C (optional), participants attend the trial site during Visit 1 (screening, Day-35 to Day-14) to undergo an eligibility check. At Visit 2, the first PET examination with radioligand will be performed at least 5 days before IMP administration. At Visit 3 (Day 1), participants receive a single dose AZD2389, then undergo a second PET examination using the radioligand on Day 2, along with blood sampling for PK analysis and FAP activity. At Visit 4 (Day 8 ±2 days), participants will be admitted to the trial site for a second single dose, then undergo a third PET examination using the radioligand on Day 9, along with blood sampling. At Visit 5 (7 days ±2 days after the PET examination on Visit 4) and Visit 6 (30 days \[+7 days\]) after the drug administration on Visit 4), follow-up visits at the trial site take place for safety monitoring and follow-up of any AEs. |
| Sequence AB | EXPERIMENTAL | Participants will receive a single dose of Treatment A (AZD2389) in Period 1 and a single dose of Treatment B (AZD2389 + quinidine) in Period 2. |
| Sequence BA | EXPERIMENTAL | Participants will receive a single dose of Treatment B (AZD2389 + quinidine) in Period 1 and a single dose of Treatment A (AZD2389) in Period 2. |
| Treatment Arm | EXPERIMENTAL | In Period 1, participants will receive midazolam and caffeine in combination on Day 1. Participants will receive bupropion on Day 2. In Period 2, participants will receive AZD2389 for 9 days from Day 5 to Day 13. In Period 3, participants will first receive AZD2389 with midazolam and caffeine in combination on Day 14. On Day 15, participants will first receive AZD2389 with bupropion. On Days 16 and 17, participants will receive AZD2389. |
| Cohort 1 | EXPERIMENTAL | Participants with normal hepatic function (sex-, age-, and body mass index \[BMI\]-matched) |
| Cohort 2 | EXPERIMENTAL | Participants with mild hepatic impairment (CP A classification) |
| Cohort 3 | EXPERIMENTAL | Participants with moderate hepatic impairment (CP B classification) |
| Cohort 4 | EXPERIMENTAL | Participants with severe hepatic impairment (CP C classification) |
| Name | Type | Description |
|---|---|---|
| AZD2389 | DRUG | 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 | OTHER | Oral administration |
| PET scan and radioligand | DIAGNOSTIC_TEST | PET scan and radioligand |
| Quinidine | DRUG | Quinidine will be administered orally. |
| Midazolam | DRUG | Single oral dose on: * Day 1 (co-administered with caffeine) * Day 14 (co-administered with caffeine and AZD2389) |
| Caffeine | DRUG | Single oral dose on: * Day 1 (co-administered with midazolam) * Day 14 (co-administered with midazolam and AZD2389) |
| Bupropion | DRUG | Single oral dose on: * Day 2 (alone) * Day 15 (co-administered with AZD2389) |
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 f...
AZD2389 is an investigational small molecule being developed by AstraZeneca for advanced chronic liver disease, hepatic impairment, and liver fibrosis. It is in clinical development, with Phase 1 and Phase 2 studies conducted in participants with liver fibrosis, hepatic cirrhosis, and healthy volunteers. It has not been approved for any indication.
AZD2389 is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca sponsors the clinical program, including the Phase 2 study in steatotic liver disease with advanced fibrosis and the completed Phase 1 pharmacokinetic and PET imaging trials.
AZD2389 is in Phase 1 development, with a Phase 2 trial also underway. The Phase 2 study, NCT07610837, is recruiting adults with steatotic liver disease and advanced fibrosis. Three Phase 1 trials have been completed, evaluating pharmacokinetics, drug interactions, and FAP occupancy in the liver.
AZD2389 has been studied in four trials. NCT07610837 is a recruiting Phase 2 study in steatotic liver disease and advanced fibrosis. Completed Phase 1 trials include NCT07069725, a PET trial measuring FAP occupancy in liver fibrosis, plus NCT06974565 and NCT06973005, which assessed pharmacokinetics and drug interactions in healthy participants.
No. AZD2389 is investigational and has not been approved by the FDA or any regulatory agency. It remains in clinical development, with a Phase 2 trial recruiting and Phase 1 trials completed. Approval would require successful completion of later-stage studies demonstrating safety and efficacy.
Across the AZD2389 clinical program, 152 participants have been enrolled in four trials. The recruiting Phase 2 study NCT07610837 plans to enroll 104 adults with steatotic liver disease and advanced fibrosis, while the completed Phase 1 trials enrolled 8 and 16 participants each.