Comparative Diagnostic Efficacy of [18F]AlF-FAPI-74 Versus [18F]FDG PET/CT in Fever of Unknown Origin, IgG4-Related Disease, and Axial Spondyloarthritis
- Trial ID
- 2024-516464-28-00
- Sponsor
- UZ Leuven
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the diagnostic performance of **[18F]AlF-FAPI-74 PET/CT** compared to the standard **[18F]FDG PET/CT** in various inflammatory disorders. Specifically, the study aims to demonstrate at least non-inferiority of [18F]AlF-FAPI-74 in the diagnostic performance for patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Additionally, it seeks to establish the superiority of [18F]AlF-FAPI-74 in assessing disease extent in patients with IgG4-related disease (IgG4-RD). Furthermore, the study aims to explore the potential of [18F]AlF-FAPI-74 in differentiating inflammatory back pain in patients with axial spondyloarthritis (axSpA) from mechanical back pain, and in evaluating treatment response in axSpA patients.
The secondary objectives include:
- For the FUO/IUO cohort, determining the distribution of major causal groups (infectious, inflammatory, malignant, and miscellaneous) and evaluating the superiority of [18F]AlF-FAPI-74 over [18F]FDG in these groups. It also involves assessing the potential of [18F]AlF-FAPI-74 to outperform [18F]FDG in larger patient cohorts and determining diagnostic accuracy metrics such as true positives and negatives.
- In the IgG4-RD cohort, conducting semi-quantitative uptake measurements and evaluating target-to-background uptake values for both tracers. The study will also assess organ detection ratios, the total number of affected organs per patient, and treatment response by quantifying changes in SUVmax.
- For axSpA, performing semi-quantitative uptake measurements in the spine and sacroiliac joints, determining mean SUVmax and TBR, and assessing statistical differences between cohorts. The study will also evaluate treatment response following a 3-month treatment with bDMARDs.
Participants
The clinical trial involves a study population comprising **adult** participants aged over 18 years, including both **male** and **female** subjects. The trial does not include a vulnerable population. The study focuses on individuals with specific medical conditions, namely **fever of unknown origin**, **IgG4-related disease**, and **axial spondyloarthritis**. Participants were selected based on their medical history and diagnostic criteria relevant to these conditions. The trial population includes individuals who have undergone or are scheduled to undergo a [18F]FDG PET/CT scan. Female participants are required to be post-menopausal, surgically sterile, or using effective contraception with a negative pregnancy test. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data. Key inclusion criteria include a high clinical suspicion of the relevant medical conditions, as determined by experienced clinicians, and specific diagnostic and clinical history requirements. The trial aims to evaluate the diagnostic performance of [18F]AlF-FAPI-74 PET/CT in comparison to [18F]FDG PET/CT across the specified cohorts.
Plans and Procedures
The clinical trial is designed to evaluate the **diagnostic performance** of the novel imaging tracer **[18F]AlF-FAPI-74** in comparison to the standard **[18F]FDG** in patients with inflammatory disorders, including **fever of unknown origin**, **IgG4-related disease**, and **axial spondyloarthritis**. This trial is structured as a prospective, randomized, double-blind, controlled study. The trial is expected to commence recruitment on June 1, 2025, and conclude by May 31, 2029, with the total duration of participant involvement varying based on individual response and condition.
Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed through screening criteria, including age, consent, and specific medical history. The primary inclusion criteria require participants to be over 18 years of age, with a confirmed or suspected diagnosis relevant to the study's focus. Female participants must meet specific reproductive health criteria. The study will include follow-up visits to monitor the diagnostic performance of the imaging tracer and assess disease progression or response to treatment. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.
The expected length of participant involvement is contingent upon the specific cohort and treatment response, with a maximum treatment period of one day for the imaging procedure. Conditions that may lead to early termination from the study include withdrawal of consent, adverse reactions to the imaging tracer, or any significant protocol deviations. The primary endpoints focus on the sensitivity of the imaging tracer in diagnosing and assessing the extent of the disease, with secondary endpoints evaluating the tracer's ability to differentiate between inflammatory and mechanical back pain. The trial aims to establish the non-inferiority or superiority of **[18F]AlF-FAPI-74** in specific diagnostic scenarios, contributing valuable insights into its potential clinical applications.
Treatment
The clinical trial involves the use of the experimental medication **[18F]FAPI-74**, which is a novel fibroblast imaging tracer. The pharmaceutical form of this medication is a **solution for injection**. The active substance, **[AL[18F]F]FAPI-74**, is of chemical origin. The medication is administered via **intravenous injection**. The dosing regimen specifies a maximum daily dose of 100 MBq (megabecquerel) and a maximum total dose of 550 MBq over the course of the treatment period, which is limited to one day. The medication is not formulated for pediatric use and is not classified as an orphan drug.
In this study, the experimental medication **[18F]FAPI-74** is compared against the standard-of-care tracer **[18F]FDG**. The trial aims to evaluate the diagnostic performance of **[18F]FAPI-74** PET/CT in various inflammatory disorders, including its potential superiority in assessing disease extent in the IgG4-related disease cohort and its ability to differentiate inflammatory back pain in patients with axial spondyloarthritis from mechanical back pain. The study also includes a follow-up scan after three months of treatment to assess treatment response in patients with axial spondyloarthritis.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the diagnostic performance of **[18F]AlF-FAPI-74** PET/CT compared to the standard **[18F]FDG** PET/CT in various inflammatory disorders. The primary endpoints include sensitivity for evaluating the origin of fever and/or inflammation in patients with Fever of Unknown Origin (FUO) or Inflammation of Unknown Origin (IUO), sensitivity for diagnosing IgG4-Related Disease (IgG4-RD) and assessing disease extent using the organ detection ratio, and sensitivity and specificity in differentiating inflammatory back pain from mechanical back pain in patients with axial spondyloarthritis (axSpA).
The trial aims to demonstrate at least non-inferiority of **[18F]AlF-FAPI-74** PET/CT over **[18F]FDG** PET/CT in the FUO cohort, superiority in the IgG4-RD cohort, and the potential to differentiate inflammatory back pain in axSpA from mechanical back pain. Efficacy assessments will be conducted through PET/CT imaging, with a second scan planned after 3 months of treatment in the axSpA cohort to evaluate treatment response. The trial will utilize the organ detection ratio as a tool for assessing disease extent in IgG4-RD patients.
Inclusion and Exclusion Criteria
Inclusion Criteria
- A. General: - 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. B. FUO - Patient underwent a [18F]FDG PET/CT or is planned to have one in the following 2 weeks. - 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. C. IgG4 - Patient underwent a [18F]FDG PET/CT or is planned to have one in the following 2 weeks. - 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 the 2019 American College of Rheumatology/European League Against Rheumatism Criteria for IgG4-related Disease, with moderate to high disease activity. D. AxSpa - 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. E. NMD a. Inflammatory neuromuscular group • Diagnosis of an inflammatory disease, particularly: o Sporadic inclusion body myositis (sIBM), or o Idiopathic inflammatory myopathies (IIM) b. Neuromuscular diseases control group • Diagnosis of one of the following acquired or hereditary neuromuscular disorders: o Glycogen storage myopathy type 2 (GSD2) o Limb-girdle muscular dystrophies (LGMD) o Becker muscular dystrophy (BMD) o Facioscapulohumeral muscular dystrophy (FSHD) o Oculopharyngeal muscular dystrophy (OPMD) o Myotonic dystrophy type 1 (DM1) o Therapy-refractory myasthenia gravis (MG) c. Healthy Control group • No known ongoing inflammatory, neuromuscular, oncological or metabolic disorders.
Exclusion Criteria
- 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. 4. NMD - None.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Jun 2025 | 192 |