Safety, Tolerability, and Biodistribution of [89Zr]Zr-DFO-APAC in Subjects With PAOD/CLI and Healthy Volunteers (Acronyms: 89Zr = Zirconium-89, DFO = Desferrioxamine, APAC = AntiPlatelet AntiCoagulant, PET/CT = Positron Emission Tomography/Computed Tomography)

NCT06204237 | Recruiting Early Phase 1

• 2 other identifiers: 2023-505287-11-0117489
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Peripheral Arterial Occlusive Disease; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Study duration (Up to 21 days)

Other Outcomes (1)

• Biodistribution and radiation dosimetry of [89Zr]Zr following administration of [89Zr]Zr-DFO-APAC

  Day 1, day 3 and day 7 after dosing

Study Arms (1)

[89Zr]Zr-DFO-APAC

EXPERIMENTAL

Drug: [89Zr]Zr-DFO-APAC; Radiation: PET/CT scan

Interventions

[89Zr]Zr-DFO-APAC DRUG

All participants will receive a single i.v. injection of \[89Zr\]Zr-DFO-APAC 15 MBq (Megabecquerel).

[89Zr]Zr-DFO-APAC

PET/CT scan RADIATION

The IMP administration will be followed by whole-body PET/CT scanning (day 1), and repeated PET/CT scans on days 3 and 7.

[89Zr]Zr-DFO-APAC

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Provision of valid informed consent and capability to communicate well with the investigator.
• Pre-menopausal woman must be willing to practise highly effective contraception for 195 days after IMP administration.
• Men must be willing to practise highly effective contraception for 105 days after IMP administration, including condom use during the first 15 days to prevent transmission of 89-Zr to a partner of childbearing potential.
• Patients should be able to understand all study-related information in Dutch.

You may not qualify if:

• 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.
• Diagnosis of autoimmune (Type 1, or latent autoimmune diabetes in adults (LADA))diabetes mellitus.
• HbA1c \>10% at screening.
• Current use of anticoagulant therapy (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban, fondaparinux, or any heparin derivative) for any medical reason.
• Patients treated with combined antiplatelet agents, excluding a single agent, such as acetylsalicylic acid (up to 100 mg QD) or clopidogrel (up to 75 mg QD).
• Use of non-steroidal anti-inflammatory medications within 2 weeks prior to dosing with \[89Zr\]Zr-DFO-APAC. If pain relief is required, paracetamol may be used.
• Use of selective serotonin reuptake inhibitor (SSRI) medications within 2 weeks prior to dosing with \[89Zr\]Zr-DFO-APAC.
• Major surgery, major trauma or any endovascular intervention within the past 90 days or organ biopsy or diagnostic angiography within the past 30 days prior to the screening visit.
• Uncontrolled arterial hypertension (persistent systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
• Hemoglobin \<8.0 mmol/L (130 g/l) (men) or \<7.5 mmol/L (120 g/l) (women) at screening, or platelet count \<150 x 109/L and leukocyte count \>12 x 109/L.
• Clinically significantly prolonged plasma prothrombin time (PT) and activated plasma partial thromboplastin time (APTT) (\> 1.2-fold).
• Patients with a medical history of heparin-induced thrombocytopenia.

Sponsors & Collaborators

• Aplagon Oy: lead
• TRACER Europe BV: collaborator

Study Sites (1)

The University Medical Center Groningen

Groningen, Netherlands

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Occlusive Disease 1; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• Schelto Kruijff, MD, Prof

  University Medical Center Groningen, NL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Verhaar, MD

CONTACT

0031622989025; anne-fleur@tracercro.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 12, 2024
• Study Start: February 1, 2024
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 30, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)