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

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Aug 2025 → ongoing

Decision date (initial)

2025-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

SOFIE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

1. Demonstrate at least non-inferiority of [18F]AlF-FAPI-74 PET/CT over [18F]FDG PET/CT in the diagnostic performance of PET/CT in the FUO cohort.
2. Demonstrate superiority of [18F]AlF-FAPI-74 PET/CT over [18F]FDG PET/CT in the diagnostic performance and assessment of disease extent in the IgG4-RD cohort.
3. Demonstrate the potential of [18F]AlF-FAPI-74 PET/CT in differentiating inflammatory back pain in patients with axSpA from mechanical back pain in patients with herniated discs and facet joints osteoarthritis, and evaluate the ability to assess treatment response in patients with axSpA by conducting a second scan after 3 months treatment.

Secondary objectives 1

1. 1. FUO/IUO cohort 1) Determine the distribution of the four major groups causing 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. 2) Evaluate for which entities [18F]AlF-FAPI-74 has the potential to outperform [18F]FDG PET/CT in larger patient cohorts. 3) Determine the ratio of true positives, true negatives, false positives, false negative, positive predictive value, and negative predictive value. 2. IgG4-RD 1) 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. 2) Target-to-background uptake values (TBR; SUV lesion divided by SUV background) for [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT, using following background organs: liver, lung, gluteus muscle, mediastinal bloodpool, bone marrow (L4 if no abnormal uptake). 3) 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. 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. 5) Evaluate the treatment response of FAPI and FDG lesions by quantifying the change in SUVmax between baseline and post-therapy PET/CT scans. 3. Axial Spondyloarthritis (axSpA) 1) 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 patients with axSpA and in patients with mechanical back pain. 2) Determine the mean SUVmax and TBR from all lesions in the spine in patients with axSpA and patients with mechanical back pain. 3) 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. 4) Assess treatment response by evaluating changes in semi-quantitative measurements (SUVmax, TBR) in patients with axSpA following 3 month treatment with bDMARDs.

Conditions and MedDRA coding

Fever of unknown origin/Inflammation of unknown origin IgG4-related disease Axial Spondyloartrhitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. FUO:-Voluntary written informed consent must be obtained prior to any screening procedures. -Subject is aged over 18 years, M/F. - Patient underwent a [18F]FDG PET/CT or is planned to have one in the following 4 weeks, and preferably in less than 2 weeks. -Female subjects should be (a) post-menopausal, or (b) surgically sterile, or (c) using effective contraceptive with negative pregnancy test. -Subjects should fulfil the criteria for classic FUO or IUO o FUO  An illness of more than 3 weeks’ duration,  Temperature exceeding 38.3°C on > 3 occasions,  Diagnosis uncertain despite appropriate first-line investigations. o IUO  An illness of more than 3 weeks’ duration,  Temperature not exceeding 38.3°C on > 3 occasions,  Raised inflammatory markers (C-reactive protein > 30mg/dL) on > 3 occasions,  Diagnosis uncertain despite appropriate first-line investigations. IgG4-RD: - Voluntary written informed consent must be obtained prior to any screening procedures. - Subject is aged over 18 years, M/F. - Patient underwent a [18F]FDG PET/CT or is planned to have one in the following 2 weeks. - Female subjects should be (a) post-menopausal, or (b) surgically sterile, or (c) using effective contraceptive with negative pregnancy test. - High clinical suspicion of IgG4-RD by an experienced clinician of Internal Medicine, based on anamnesis, physical examination, first-line investigations and blood tests. - Relapse of diagnosed IgG4-RD on histopathology, according to the 2019 American College of Rheumatology/European League Against Rheumatism Criteria for IgG4-related Disease, with moderate to high disease activity. AxSpA: - Voluntary written informed consent must be obtained prior to any screening procedures. - Subject is aged over 18 years, M/F. - Female subjects should be (a) post-menopausal, or (b) surgically sterile, or (c) using effective contraceptive with negative pregnancy test. - For the inflammatory back pain cohort: o 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). o 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. - For the mechanical back pain cohort: o Lower back pain of mechanical origin (discus, fact joint, …), confirmed by MRI findings of the lumbar spine. o Not caused by trauma.

Exclusion criteria 1

1. 1 General exclusion criteria. Participants eligible for this Investigation must not meet any of the following criteria: - Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity beginning 4 days prior to tracer injection up to 1 day after tracer injection. - Subject does not understand the study procedures. - Subject is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator. - Subject has had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months. - Subject does not agree that incidental findings are communicated to the general practitioner and to the participant him/herself. - If applicable: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. 2. Specific exclusion criteria 1. FUO/IUO - None 2. IgG4-RD - Treatment for IgG4-RD already commenced before study scan or [18F] FDG PET/CT. 3. AxSpA - Treatment with bDMARDS already commenced before study scan.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. FUO/IUO: sensitivity for evaluating the origin of fever and/or inflammation. 2. sensitivity for diagnosing IgG4-RD in patients with suspected IgG4-RD and assessment of disease extent in patients with confirmed IgG4-RD using the organ detection ratio. 3. AxSpA: sensitivity and specificity in differentiating inflammatory back pain from mechanical back pain.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Koen Van Laere

Public contact point

Organisation

UZ Leuven

Contact name

Koen Van Laere

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications