The goal of this Phase 0 clinical trial is to evaluate safety and biodistribution of \[89Zr\]Zr-DFO-APAC in patients with peripheral arterial occlusive disease / critical limb ischemia (PAOD/CLI) and healthy volunteers. The main questions it aims to answer are:
* What is the safety, tolerability and pharmacokinetic profile (PK: both systemic and local vascular injury site-specific PK) of \[89Zr\]Zr-DFO-APAC? * What is the biodistribution and internal radiation dosimetry of the tracer dose of \[89Zr\]Zr-DFO-APAC? * What is the binding and retention time of \[89Zr\]Zr-DFO-APAC to arteries and atherosclerotic or microvascular lesions? Participants will receive a dose of the \[89Zr\]Zr-DFO-APAC (IMP) and PET/CT imaging is performed on days 1, 3 and 7, and follow-up visit 7-14 days post IMP dosing.
Males and females aged 40-85 years.
PAOD/CLI patients Rutherford categories 1-4 and category 5 with Wlfl wound grade of 0 or 1.
Estimated glomerular filtration rate (eGFR) >46 mL/min/1.73 m2 as per calculation of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
CT angiography with contrast agent performed of within 3 months of the patients' first PET-scan as part of diagnostics of PAOD, with results available in the subject's medical records.
Acute limb-threatening ischemia (e.g., embolic disease).
An existing aneurysm that requires surgical intervention.
Medical history of, or condition known to be associated with impaired hemostasis, such as an increased intracranial bleeding risk e.g., previous history of intracranial hemorrhage, subarachnoidal bleeding, hemorrhagic stroke, or gastrointestinal or retroperitoneal bleeding, or any inherited or acquired bleeding disorder, such as von Willebrand disease or hemophilia.
Any cerebrovascular event (including transient ischemic attack, thrombotic or embolic stroke) within the past year.
Single group
[89Zr]Zr-DFO-APAC
DrugAll participants will receive a single i.v. injection of \[89Zr\]Zr-DFO-APAC 15 MBq (Megabecquerel).
PET/CT scan
RadiationThe IMP administration will be followed by whole-body PET/CT scanning (day 1), and repeated PET/CT scans on days 3 and 7.
Incidence of treatment emergent adverse events (AE) (safety and tolerability)
Occurrence and severity of one or more treatment-emergent AEs from the time of i.v. administration of \[89Zr\]Zr-DFO-APAC until the end of the follow-up period, and changes in plasma/serum clinical chemistry, hematology, coagulation variables, vital signs, ECG, and physical examination findings.
Biodistribution and radiation dosimetry of [89Zr]Zr following administration of [89Zr]Zr-DFO-APAC
Dosimetry estimates and cumulated radioactivity exposure by source region and the entire body in the first three participants including analysis of radioactivity in venous blood.
Click on the lead sponsor to view all of their trials.
Aplagon Oy
Lead sponsor
TRACER Europe BV
Collaborator
