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

Cross-over, Randomized, Open-label, Single-centre, Phase II Clinical Trial to Investigate 18F-AzaFol in the Diagnosis of Large Vessel Vasculitis

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.

Study Overview

• Status: Recruiting
• Conditions: Giant Cell Arteritis
• Intervention / Treatment: Drug: AzaFol; Drug: FDG

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 Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Britta Maurer; Phone Number: +41 31 63 2 7229; Email: RI-Studien@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Rheumatology and Immunology, University Hospital Bern, Inselspital
    • Contact: Britta Maurer, Prof. Dr. med.; Phone Number: +41 31 63 2 72 29; Email: RI-Studien@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AzaFol first, FDG second; AzaFol PET/CT imaging followed by FDG PET/CT imaging (standard of care)	Drug: AzaFol; AzaFol-PET/CT imaging; Drug: FDG; FDG-PET/CT imaging
Active Comparator: FDG first, AzaFol second; FDG PET/CT imaging (standard of care) imaging followed by AzaFol PET/CT	Drug: AzaFol; AzaFol-PET/CT imaging; Drug: FDG; FDG-PET/CT imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specificity of the GCA-diagnosis at the patient level	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	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion detection rate (visual analysis)	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.	Baseline
Lesion detection rate (semiquantitative analysis)	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.	Baseline
Sensitivity of the GCA-diagnosis at the patient level	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.	Baseline

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: Paul Scherrer Institut, Center for Proton Therapy
• Investigators: Principal Investigator: Britta Maurer, Department of Rheumatology and Immunology, Inselspital, University of Bern, Bern, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PET imaging; Tracer
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Vasculitis, Central Nervous System; Arteritis; Skin and Connective Tissue Diseases; Giant Cell Arteritis
• Other Study ID Numbers: CRAFT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No