The Investigators Will Evaluate the Diagnostic Performance of [18F]-AlF-FAPI-74 PET/CT in Inflammatory Disorders and Compare it With the Current Gold Standard for Inflammation, FDG PET/CT, in Three Patient Cohort: Patients Presenting With Fever of Unknown Origin, IgG4-RD and AxSpA.

NCT07535554 | Recruiting Phase 2

• 1 other identifier: S69207 - 2024-516464-28
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study to evaluate the performance of new \[18F\]-AlF-FAPI-74 PET/CT in three inflammatory disorders (fever of unknown origin, IgG4-related disease and axial spondyloarthritis) and compare with the current stand-of-care \[18F\]-FDG PET/CT

Conditions

Fever of Unknown Origin; IgG4 Related Disease; Axial Spondylarthritis (axSpA); Inflammation of Unknown Origin

Outcome Measures

Primary Outcomes (3)

• FUO/IUO: Demonstrate that the diagnostic performance of [18F]AlF-FAPI-74 PET/CT is equivalent or superior to the current gold standard, [18F] FDG PET/CT, in contributing to the final diagnosis (non-inferiority study with non-inferiority limit (10%)

  6 months after completion of both PET/CT scans

• IgG4-RD: Demonstrate that the diagnostic performance of [18F]AlF-FAPI-74 PET/CT is superior to [18F]FDG PET/CT, in patients with suspicion of IgG4-RD and assessment of disease extent in patients with confirmed or relapsed IgG4-RD.

  After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.

• Axial Spondyloarthritis: evaluate the diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT in differentiating inflammatory back pain in patients with axSpA from patients with mechanical back pain, and evaluate the ability to assess treatment response

  After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment

Secondary Outcomes (10)

• FUO/IUO: Determine the distribution of the four major causal group in FUO/IUO (infectious, inflammatory, malignant, and miscellaneous) of both tracers and evaluate for which causal groups [18F]AlF-FAPI-74 PET/CT is superior to [18F]FDG PET/CT.

  6 months after completion of all PET/CT scans

• FUO/IUO: Evaluate for which entities [18F]AlF-FAPI-74 has the potential to outperform [18F]FDG PET/CT in lager patient cohorts.

  6 months after completion of all PET/CT scans

• FUO/IUO: Determine the ratio of true positives, true negatives, false positives, false negative, positive predictive value, and negative predictive value.

  6 months after completion of all PET/CT scans

• IgG4-RD: Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV (SUVmean), peak SUV (SUVpeak) of lesions on [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT.

  After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.

• IgG4-RD: Evaluate the organ detection ratio for every organ, defined as the percentage of patients with pathological uptake in that specific organ by each tracer for the total of number of patients with pathological uptake in that organ

  After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.

Study Arms (3)

FUO/IUO

EXPERIMENTAL

Diagnostic Test: [18F]AlF-FAPI-74 PET/CT

IgG4-related disease

EXPERIMENTAL

Diagnostic Test: [18F]AlF-FAPI-74 PET/CT

Axial Spondyloarthritis

EXPERIMENTAL

Diagnostic Test: [18F]AlF-FAPI-74 PET/CT

Interventions

[18F]AlF-FAPI-74 PET/CT DIAGNOSTIC_TEST

A \[18F\]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven). The patient will get an IV line, through which the \[18F\]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. If the patient receives therapy (for IgG4-RD and AxSpA), a second \[18F\]AlF-FAPI-74 PET/CT will be performed three months later.

Axial Spondyloarthritis; FUO/IUO; IgG4-related disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An illness of more than 3 weeks' duration,
• Temperature exceeding 38.3°C on \> 3 occasions, or elevated inflammatory markers on \> 3 occasions
• Diagnosis uncertain despite appropriate first-line investigations.
• High clinical suspicion of IgG4-RD by an experienced clinician of Internal Medicine, based on anamnesis, physical examination, first-line investigations and blood tests.
• Patients with a new diagnosis of IgG4-RD on histopathology and need for further assessment of disease extent with PET/CT,
• Relapse of diagnosed IgG4-RD on histopathology according to an experienced clinician of Internal Medicine
• High clinical suspicion of axial spondyloarthropahy according to an experienced rheumatology (based on inflammary back pain \> 3 months, insidious onset, morning stifness, improvement with exercise and worsening in rest, pain worse at night, age at onset \<45 years of age, imaging findings).
• Patient has persisting inflammatory back pain after 2 different types of NSAID's (tried for over 2-4 weeks), and is therefore eligible for biological DMARDS therapy.

You may not qualify if:

• Participant is mentally or legally incapacitated, doesn't understand the study design or is not willing or capable to undergo all study-specific procedures.
• Any disorder or condition, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
• Female who is pregnant (urinary hCG test will be performed in every WOCBP), breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive (with a relatively high Pearl Index: natural methods, minipill outside postpartum period, spermicides or condoms in monotherapy or no usage of contraception when sexually active are not accepted).
• Participation in an interventional Trial with an investigational medicinal product (IMP) or device when the trial designs are not considered compatible by the study team.
• Participation in a clinical scientific study in the last 12 months with a radiation exposure caused by the experimental procedures greater than 1 mSv.
• Participant has a known hypersensitivity to \[18F\]AlF-FAPI-74 or the used excipients.
• Active treatment has already commenced

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospital Leuven

Leuven, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Fever of Unknown Origin; Immunoglobulin G4-Related Disease

Condition Hierarchy (Ancestors)

Fever; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Lennert Boeckxstaens, MD

CONTACT

+0032 16 34 37 15; lennert.boeckxstaens@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, non-randomized, single center, multi-cohort, interventional phase II/III trial. The three cohorts are: Fever or inflammation of unknown origin (FUO/IUO), IgG4-related disease (IgG4-RD) and Axial Spondyloarthritis (AxSpA).

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: April 17, 2026
• Study Start: September 17, 2025
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)