Evaluation of 68Ga-FAPI-46 and Gallium (68Ga) Chloride PET/CT Imaging in Chronic Inflammatory and Fibrotic Disorders

The primary objective of the study is to describe the sites and **fixation intensity** of [68Ga] Ga-FAPI PET/CT examinations performed at M0 in 13 targeted chronic inflammatory and/or fibrosing diseases. This is clinically relevant as it aims to enhance the understanding of disease localization and activity in these conditions, potentially improving diagnostic accuracy and treatment planning.

Secondary objectives include: - Studying the correlation between [68Ga] Ga-FAPI PET/CT fixation intensity and the reference pathology assessment score specific to each study population. - Investigating the correlation between [68Ga] Ga-FAPI PET/CT fixation intensity and other pathology assessment parameters, main biomarkers, functional parameters, and imaging characteristics of the pathology. - Describing the evolution of [68Ga] Ga-FAPI PET/CT parameters between M0 and M3. - Comparing the results of [68Ga] Ga-FAPI PET/CT and [18F] F-FDG PET/CT at M0. - Studying the kinetics of [68Ga] Ga-FAPI tracer uptake in PET according to different pathologies and their phenotypic characteristics. - Examining the correlation between [68Ga] Ga-FAPI PET/CT fixation intensity and quality of life in inflammatory pathologies. - Analyzing the correlation between [68Ga] Ga-FAPI PET/CT fixation intensity and overall disease assessment.

The clinical trial involves participants diagnosed with **inflammatory disorders**. The study population includes both male and female subjects aged 18 years and older. Participants are required to be affected by one of the specific pathologies targeted by the study and must meet the consensus classification criteria for their respective conditions. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include satisfying the corresponding clinical situation for the pathology under investigation. No specific lifestyle considerations such as diet or physical activity are mentioned as part of the trial's inclusion or exclusion criteria.

The clinical trial is designed to evaluate the efficacy of **68Gallium-FAPI PET/CT imaging** in patients with chronic inflammatory and fibrotic diseases. This is a **randomized, double-blind, controlled** trial, categorized as a Phase 4 study. The trial aims to describe the sites and fixation intensity of **[68Ga] Ga-FAPI PET/CT** examinations at baseline in 13 targeted chronic inflammatory and/or fibrosing diseases. The primary endpoint is the binding intensity in PET, measured by the Standardized Uptake Value (SUV) max. Secondary endpoints include various measurements of fixation intensity and pathology-specific scores, biomarkers, functional parameters, imaging characteristics, and tracer uptake kinetics.

The trial is expected to commence recruitment on October 1, 2024, and conclude by October 21, 2026. Participants will be involved in the study for a maximum treatment period of one day, with a maximum total dose of 400 MBq of the radioactive tracer administered as an injectable solution. The study visits include an initial screening visit to confirm eligibility based on criteria such as age (18 or over) and diagnosis of one of the pathologies concerned by the study. Follow-up visits will be scheduled to monitor the primary and secondary endpoints, with the end-of-study visit marking the completion of the participant's involvement.

Participants may be withdrawn from the study if they do not meet the inclusion criteria, experience adverse reactions, or withdraw consent. The trial is not a low-intervention study and is exploratory and confirmatory in nature, focusing on therapeutic outcomes. The study is conducted under the auspices of the Centre Hospitalier Régional et Universitaire de Brest, utilizing **GALLIUM (68GA) CHLORIDE** and **68-FAPI-46** as the investigational products. The trial's methodology ensures rigorous assessment of the imaging technique's potential in diagnosing and managing inflammatory disorders.

The clinical trial involves the use of two experimental medications, both serving as **radioactive tracers** for imaging purposes. The first experimental medication is **GALLIUM (68GA) CHLORIDE**, which is administered as a **solution for injection**. The active substance, **gallium (68Ga) chloride**, is of chemical origin. The dosage is measured in megabecquerels (MBq), with a maximum daily dose of 200 MBq and a total maximum dose of 400 MBq. The administration route is via injection, and the treatment period is limited to a single day. This medication is not formulated for pediatric use and is not classified as an orphan drug.

The second experimental medication is **68-FAPI-46**, also administered as an **injectable solution**. The active substance is a complex chemical compound, specifically (S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethylcarbamoyl)-quinolin-6-yl)(methyl)amino)-propyl)piperazin-1-yl)-2-oxoethyl)-68Ga-[1,4,7,10]-tetraazacyclododecane-1,4,7-triyl)triacetate. Similar to the first medication, the dosage is capped at 200 MBq per day, with a total maximum dose of 400 MBq, and the treatment duration is one day. This medication is also not intended for pediatric use and is not designated as an orphan drug.

Both medications are utilized in the context of the PARADISE study, which aims to evaluate the sites and fixation intensity of [68Ga] Ga-FAPI PET/CT examinations in chronic inflammatory and fibrotic diseases. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial data. Participant compliance with the dosing schedule is monitored to ensure adherence to the specified administration guidelines.

Efficacy in the clinical trial titled "68Gallium-FAPI PET/CT imaging in Chronic inflammatory and fibrotic diseases (PARADISE study)" will be assessed using both primary and secondary endpoints. The primary endpoint involves the measurement of **binding intensity** in PET, specifically quantified by the Standardized Uptake Value (SUV) max. This parameter will provide a quantitative assessment of tracer uptake, reflecting the degree of fixation intensity in the targeted tissues.

Secondary endpoints are designed to further explore the efficacy of the intervention across various dimensions. These include the measurement of fixation intensity in PET and the evaluation of pathology-specific reference scores, biomarkers, functional parameters, and imaging characteristics, where applicable. Additionally, the study will assess the uptake kinetics of the [68Ga] Ga-FAPI tracer in PET according to different pathologies and their phenotypic characteristics. The study will also compare the fixation intensity of [68Ga] Ga-FAPI PET/CT with [18F] F-FDG PET/CT at baseline (M0). Furthermore, the efficacy assessment will incorporate patient-reported outcomes through the SF-36 questionnaire score and a global disease assessment.