AZD2389 effect on liver FAP binding in people with advanced liver fibrosis.

A Phase 1, Open-label Positron Emission Tomography Trial to Assess Changes in Liver Uptake of [68Ga]Ga-FAPI-46 Following Oral Administration of Single Doses of AZD2389 to Patients With Advanced Liver Fibrosis (PECHORA).

We will test whether a drug called AZD2389 changes how much FAP it binds in the livers of adults with advanced liver fibrosis using PET scans.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 2 sites (Solna and 1 other locations)
• Trial ID: NCT07069725 on ClinicalTrials.gov

What this trial studies

This is a phase 1, open-label PET trial enrolling adults with compensated advanced liver fibrosis or cirrhosis to measure target engagement of AZD2389 in the liver. The trial uses an adaptive design with up to three sequential panels: a pilot panel, a main panel with three ascending dose levels (two participants per dose), and an optional panel. Participants will receive AZD2389 and undergo PET imaging with a radioligand to quantify fibroblast activation protein (FAP) occupancy, plus safety and laboratory monitoring. The study excludes people with decompensated cirrhosis, active viral infections (HBV, HCV, HIV), significant kidney impairment, or other conditions that would interfere with imaging or safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 20 or older with compensated advanced liver fibrosis or cirrhosis, able to consent, not of childbearing potential, and without active viral hepatitis, significant kidney impairment, or recent major illness or surgery.

Not a fit: People with decompensated cirrhosis, active hepatitis B/C or HIV, low platelets, poor kidney function, pregnancy, or other conditions that interfere with PET imaging or safety are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the study could show that AZD2389 reaches and occupies FAP in the liver, information that would guide further development of anti-fibrotic therapies.

How similar studies have performed: FAP-targeting PET occupancy approaches have been used in other research areas such as oncology, but using AZD2389 to measure liver FAP occupancy in advanced fibrosis is a novel, early-stage application.

Eligibility criteria

Key Inclusion Criteria:

1. 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.
2. History confirming compensated liver cirrhosis.
3. Females must have a negative pregnancy test.
4. Barrier contraceptives use by males.

Key Exclusion Criteria:

1. 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.
2. Any clinically significant illness, medical or major surgical procedure or trauma prior randomization.
3. Hepatitis B , hepatitis C and/or HIV infection.
4. Significant elevations in liver blood test, MELD score \>12 and platelets \<100 x109/L g).
5. eGFR) \< 60 ml/min/1.73m2.
6. History of decompensated liver cirrhosis.
7. Any participants with an aetiology of liver cirrhosis where the Investigator considers that PET signal uptake may be impacted.
8. History of bleeding disorders and major bleeding risk.
9. History of severe dermatological disorders or wound healing.
10. Positive screening result for drugs of abuse or alcohol.

Where this trial is running

Solna and 1 other locations

• Research Site — Solna, Sweden (Withdrawn)
• Research Site — Stockholm, Sweden (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Liver Fibrosis; Hepatic Cirrhosis