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.

Official title

Prospective Diagnostic Performance of PET/CT Using the Novel Fibroblast Imaging Tracer [18F]-AlF-FAPI-74 Versus Standard of Care [18F]-FDG in Inflammatory Disorders

Overview

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

Interventions

• Diagnostic test [18F]AlF-FAPI-74 PET/CT
  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-

Primary outcome measures

• 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%) [Time frame: 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. [Time frame: 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 [Time frame: After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment]

Secondary outcome measures (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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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 [Time frame: 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: 4) Evaluate the total number of affected organs per patient for each tracer and calculate the difference for both tracers. Determine the total difference of affected organs between both tracers for all patients. [Time frame: 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 treatment response of FAPI and FDG lesions by quantifying the change in SUVmax between baseline and post-therapy PET/CT scans. [Time frame: After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.]
• AxSpA: Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), target-to-background (TBR)) of lesions in the spine and the sacro-iliac joints will be computed on [18F]AlF-FAPI-74 PET/CT in all patients [Time frame: After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment]
• AxSpA: Determine if there is a significant statistical difference (p<0.05) in semi-quantitative uptake measurements (SUVmax, TBR) between the two cohorts, and determine the optimal cut-off value. [Time frame: After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment]
• AxSPa: Assess treatment response by evaluating changes in semi-quantitative measurements (SUVmax, TBR) in patients with axSpA following 3 month treatment with bDMARDs. [Time frame: After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment]

Eligibility criteria

Inclusion Criteria FUO:

• 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.

Inclusion criteria IgG4-RD:

• 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

Inclusion criteria AxSpA:

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Belgium · 1 center

• University Hospital Leuven — Leuven

Identifiers

NCT: NCT07535554 · S69207 - 2024-516464-28

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗