Fever of Unknown OriginPhase 2/3NCT07535554
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.
A Phase 2/3 study testing [18F]AlF-FAPI-74 PET/CT in people with Fever of Unknown Origin and IgG4 Related Disease, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fever of Unknown Origin, IgG4 Related Disease, Axial Spondylarthritis (axSpA)
- What is being tested?
- [18F]AlF-FAPI-74 PET/CT
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteBelgium
- Study dates
- 17 Sep 2025to 31 Mar 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
University Hospital Leuven
Leuven, 3000
Lennert Boeckxstaens, MD, 0032 1634 37 15, lennert.boeckxstaens@uzleuven.be
About this study
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
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
- Being tested
- [18F]AlF-FAPI-74 PET/CT
- Medical subject headings
- Fever of Unknown Origin, Immunoglobulin G4-Related Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]AlF-FAPI-74 PET/CTDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| FUO/IUO | Experimental | Not described Receives: Diagnostic Test: [18F]AlF-FAPI-74 PET/CT |
| IgG4-related disease | Experimental | Not described Receives: Diagnostic Test: [18F]AlF-FAPI-74 PET/CT |
| Axial Spondyloarthritis | Experimental | Not described Receives: Diagnostic Test: [18F]AlF-FAPI-74 PET/CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%)
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2026
- Study start17 Sep 2025
- Primary completion31 Mar 2029 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fever of Unknown OriginStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- 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).
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07535554
- Sponsor's protocol ID
- S69207 - 2024-516464-28
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2026
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07535554
- Acronym / sponsor ID
- S69207 - 2024-516464-28
- Conditions
- Fever of Unknown Origin, IgG4 Related Disease, Axial Spondylarthritis (axSpA), Inflammation of Unknown Origin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 17 Sep 2025 (actual)
- Primary completion
- 31 Mar 2029 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 17 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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,
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]AlF-FAPI-74 PET/CTA [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. | Diagnostic test | Axial Spondyloarthritis, FUO/IUO, IgG4-related disease |
Primary outcome
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
10 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing [18F]AlF-FAPI-74 PET/CT in people with Fever of Unknown Origin and IgG4 Related Disease, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lennert Boeckxstaens, MD (+0032 16 34 37 15, lennert.boeckxstaens@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.