A Clinical Trial to Investigate 18F-AzaFol in the Diagnosis of Large Vessel Vasculitis

Phase 2

Recruiting

• Conditions: Giant Cell Arteritis
• Interventions: Drug: AzaFol; Drug: FDG

• Registration Number: NCT06335888
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

The goal of this open-label clinical trial is to evaluate the efficacy of AzaFol-PET/CT in the diagnosis of GCA (giant cell arteritis), to compare AzaFol- with 2-\[18F\]FDG-PET/CT, and to assess the safety and tolerability of AzaFol in subjects with suspicion of GCA.

Participants will undergo AzaFol-PET/CT imaging at a single timepoint.

Detailed Description

Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly population. 2-\[18F\]Fluor-2-desoxy-D-glucose (2-\[18F\]FDG) positron emission tomography (PET)/ computed tomography (CT) is performed to diagnose GCA (standard of care, SOC) but unable to reliably distinguish atherosclerosis from vasculitis. Activated macrophages express folate receptor (FR)-β and are enriched in inflamed vascular tissue in GCA. 3'-Aza-2'-\[18F\]Fluoro-Folic Acid (AzaFol) is a nuclear tracer targeting FRβ. The investigators hypothesize that AzaFol is a specific and reliable tracer to visualize activated macrophages in GCA and therefore might improve the discrimination of vasculitic and atherosclerotic lesions as compared to 2-\[18F\]FDG-PET/CT.

Study Timeline

• Study First Submitted: 2024-03-21
• Study First Submitted QC: 2024-03-21
• Study First Posted: 2024-03-28
• Status Verified: 2025-02
• Study Start: 2025-02-03
• Last Update Submitted: 2025-02-12
• Last Update Posted: 2025-02-13
• Primary Completion: 2029-05
• Study Completion: 2029-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Individuals ≥ 50 years with clinical suspicion of GCA
• Women of childbearing potential must not have a positive serum pregnancy test at the Screening Visit
• Subjects must be able to understand and adhere to all protocol requirements and must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
• Are willing and able to comply with procedures required in this protocol.

Exclusion Criteria

1. Folate deficiency
2. Female subjects who are pregnant, breastfeeding, or considering becoming pregnant during the study or within 30 days after the last dose of study drug
3. Concomitant treatment with medications that lead to a significant impairment of folic acid levels (methotrexate, pemetrexed, raltitrexed)
4. Concomitant glucose-containing infusion or parental nutrition within 6 hours prior to 2-[18F]FDG tracer application
5. Glucose level > 10 mmol/l at the timepoint of 2-[18F]FDG PET/CT
6. Unable to remain in the PET/CT for the duration of the examination
7. Unable to lie still for the duration of the examination (45 min)
8. Unable not to eat or drink (except water) for 6 hours prior to 2-[18F]FDG tracer application
9. Prior PET-imaging within 60 days before baseline
10. Intake of vitamin supplements containing > 1mg/day folic acid within 48 h prior to the PET/CT with AzaFol
11. Known hypersensitivity or allergy to folic acid
12. Enrolment of the investigator, his/her family members, employees and other dependent persons
13. Participation in another study with investigational drug within the 7 days preceding and during the present study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AzaFol first, FDG second	FDG	AzaFol PET/CT imaging followed by FDG PET/CT imaging (standard of care)
AzaFol first, FDG second	AzaFol	AzaFol PET/CT imaging followed by FDG PET/CT imaging (standard of care)
FDG first, AzaFol second	AzaFol	FDG PET/CT imaging (standard of care) imaging followed by AzaFol PET/CT
FDG first, AzaFol second	FDG	FDG PET/CT imaging (standard of care) imaging followed by AzaFol PET/CT

Primary Outcome Measures

Name	Time	Method
Specificity of the GCA-diagnosis at the patient level	Baseline	Specificity of the GCA-diagnosis at the patient level using visual analysis as a diagnostic method with the clinical expert diagnosis as the reference standard

Secondary Outcome Measures

Name	Time	Method
Lesion detection rate (visual analysis)	Baseline	Lesion detection rate in PET/CT in patients with suspicion of GCA, in patients with GCA (clinical expert diagnosis), and in patients without GCA (clinical expert diagnosis) by visual analysis at the level of the vessel.
Lesion detection rate (semiquantitative analysis)	Baseline	Lesion detection rate in PET/CT in patients with suspicion of GCA, in patients with GCA (clinical expert diagnosis), and in patients without GCA (clinical expert diagnosis) by semiquantitative analysis at the level of the vessel.
Sensitivity of the GCA-diagnosis at the patient level	Baseline	Sensitivity of the GCA-diagnosis at the patient level using visual evaluation as a diagnostic method with the clinical expert diagnosis as the reference standard.

Trial Locations

Locations (1)

Department of Rheumatology and Immunology, University Hospital Bern, Inselspital; 🇨🇭 Bern, Switzerland