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.
This is a phase 1, open-label, PET trial in male and female patients with advanced liver fibrosis. The trial will consist of up to 3 sequential panels: Part A (Pilot panel), Part B (Main panel - 3 dose levels of AZD2389, 2 participants per dose level.), and Part C (optional panel). The design of the trial is adaptive and adjustments in time points and/or number of assessments and samples can be made during the course of the trial.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Doses of AZD2389 will be administrated orally
PET scan and radioligand
Research Site
Stockholm, Sweden
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.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
Plasma concentrations of AZD2389.
To evaluate plasma PK of AZD2389 after single doses.
Time frame: 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)
Blood sampling and analysis to evaluate PK plasma of AZD2389 after single doses.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
% FAP inhibition compared to baseline in plasma.
To evaluate the plasma target engagement of AZD2389 by assessment of plasma FAP inhibition following single oral dosing.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
% aTRV (for radioligand uptake).
To quantify test-retest reproducibility of radioligand \[68Ga\]Ga-FAPI-46 uptake in the liver.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
ICC (for radioligand uptake).
To quantify test-retest reproducibility of radioligand \[68Ga\]Ga-FAPI-46 uptake in the liver.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
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Maximum possible target occupancy (Occmax).
A theoretical relationship between average concentration of AZD2389 in plasma during the PET examination and radioligand binding will be assumed to calculate maximum target occupancy, if possible, by curve fitting.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)
The IC50 confidence interval
A theoretical relationship between average concentration of AZD2389 in plasma during the PET examination and radioligand binding will be assumed to calculate the confidence interval associated with the IC50.
Time frame: PART B: Day 7(+/-2 days); PART C: Day 2 and Day 8 (+/-2 days)