Axial Spondylarthritis (axSpA), Fever of Unknown Origin, IgG4 Related Disease, Inflammation of Unknown Origin
Conditions
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
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-FAPI-74 PET/CT will be performed three months later.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
| 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. | 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. | 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 | 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. | 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. | After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment |
Countries
Belgium
Contacts
CONTACTLennert Boeckxstaens, MD
Outcome results
None listed