The Phase 1, Open-label, PET Trial Designed to Investigate the Effect of AZD2389 on FAP Occupancy in the Liver in Participants With Advanced Liver Fibrosis.

NCT07069725 | Recruiting Phase 1

• 1 other identifier: D7930C00003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 1, open-label, PET trial. The study is designed to investigate the effect of AZD2389 on FAP occupancy in the liver in participants with advanced liver fibrosis.

Conditions

Liver Fibrosis; Hepatic Cirrhosis

Keywords

Liver Fibrosis; Hepatic Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Occupancy, %: percent change from baseline in uptake of FAP PET radioligand [68Ga]Ga-FAPI-46 in the liver after a single dose of AZD2389.

  To examine target FAP occupancy in the liver by AZD2389 as measured with \[68Ga\]Ga-FAPI-46 PET.

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

Secondary Outcomes (7)

• Plasma concentrations of AZD2389.

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

• AZD2389 PK parameters calculated by: the plasma concentration vs. time curve (AUC) from 0 to infinity (AUCinf) and maximum observed concentration (Cmax)

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

• % FAP inhibition compared to baseline in plasma.

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

• % aTRV (for radioligand uptake).

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

• ICC (for radioligand uptake).

  PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)

Study Arms (5)

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.

Diagnostic Test: PET scan and radioligand

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.

Drug: AZD2389; Diagnostic Test: PET scan and radioligand

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.

Drug: AZD2389; Diagnostic Test: PET scan and radioligand

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.

Drug: AZD2389; Diagnostic Test: PET scan and radioligand

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.

Drug: AZD2389; Diagnostic Test: PET scan and radioligand

Interventions

AZD2389 DRUG

Doses of AZD2389 will be administrated orally

Part B1; Part B2; Part B3; Part C

PET scan and radioligand DIAGNOSTIC_TEST

PET scan and radioligand

Also known as: The participants will perform the PET examination at the PET Centre using the radioligand [68Ga]Ga-FAPI-46.

Part A; Part B1; Part B2; Part B3; Part C

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female (of non-childbearing potential) participant aged ≥ 20 years and willing and able to give written informed consent for participation in the trial.
• History confirming compensated liver cirrhosis.
• Females must have a negative pregnancy test.
• Barrier contraceptives use by males.

You may not qualify if:

• A condition that would interfere with evaluation of the trial intervention, put the participant at risk, influence the participant's ability to participate or affect the interpretation of the results of the trial.
• Any clinically significant illness, medical or major surgical procedure or trauma prior randomization.
• Hepatitis B , hepatitis C and/or HIV infection.
• Significant elevations in liver blood test, MELD score \>12 and platelets \<100 x109/L g).
• eGFR) \< 60 ml/min/1.73m2.
• History of decompensated liver cirrhosis.
• Any participants with an aetiology of liver cirrhosis where the Investigator considers that PET signal uptake may be impacted.
• History of bleeding disorders and major bleeding risk.
• History of severe dermatological disorders or wound healing.
• Positive screening result for drugs of abuse or alcohol.

Sponsors & Collaborators

• AstraZeneca: lead
• Karolinska Institutet: collaborator
• CTC Clinical Trial Consultants AB: collaborator

Study Sites (2)

Research Site

Solna, 171 64, Sweden

WITHDRAWN

Research Site

Stockholm, 17176, Sweden

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label trial.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Groups of participants are assigned to receive interventions based on prior milestones being reached in the study, such as in some dose escalation and adaptive design studies.

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: July 17, 2025
• Study Start: May 26, 2025
• Primary Completion (Estimated): July 13, 2026
• Study Completion (Estimated): July 13, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• 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 refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• 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.

Locations

SE (2)