Evaluation of [18F]Fluoro-PEG-Folate PET-CT for Assessing Anti-TNF Therapy Response in Rheumatoid Arthritis Patients

The primary objective of this study is to investigate the association between quantitative changes in whole body **[18F]PEG Folate PET/CT** imaging after 4 weeks and the clinical response to anti-TNF therapy at 26 weeks of treatment in patients with clinically active established **Rheumatoid Arthritis**. This objective is clinically relevant as it aims to determine the potential of **[18F]PEG Folate PET/CT** as a predictive tool for evaluating the effectiveness of anti-TNF therapy, which could lead to more personalized treatment strategies for patients with **Rheumatoid Arthritis**.

The clinical trial involves participants diagnosed with **Rheumatoid Arthritis**. The study population includes both male and female subjects, aged 30 years and older, who have clinically active disease as assessed by a physician. The trial does not involve a vulnerable population. Participants are required to have arthritis in at least one joint accessible to synovial biopsy and a clinical indication to (re)start anti-TNF therapy. Prior treatment with one anti-TNF agent is permitted, provided there was no primary failure. The trial allows the use of disease-modifying anti-rheumatic drugs (DMARDs) and oral corticosteroids up to 10 mg daily, as well as non-steroidal anti-inflammatory drugs (NSAIDs), given that the doses are stable for at least four weeks prior to inclusion and during the study. Participants must be able to adhere to study appointments and protocol requirements, and informed consent must be obtained prior to study-related procedures. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the effectiveness of **[18F]Fluor-PEG-Folate** as a PET tracer for monitoring therapy response in patients with **Rheumatoid Arthritis**. This is a phase 2 trial, focusing on the association between quantitative changes in whole-body **[18F]PEG Folate PET/CT** imaging after four weeks and the clinical response to anti-TNF therapy at 26 weeks. The study employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to run from May 2022 to June 2026, with participant involvement lasting up to 26 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and previous treatment history. Following the screening, participants will receive the investigational product via **intravenous infusion**. Subsequent visits will occur at regular intervals to monitor the response to treatment, with a primary endpoint assessment at 26 weeks. The end-of-study visit will conclude the participant's involvement, where final assessments and data collection will occur.

The expected length of participant involvement is approximately 26 weeks, with conditions for early termination including non-compliance with study protocols or adverse reactions to the investigational product. Participants must adhere to stable doses of permitted medications, such as DMARDs and NSAIDs, throughout the study. The trial aims to provide valuable insights into the diagnostic potential of the tracer in visualizing and quantifying TNF expression in inflamed joints, contributing to the understanding of treatment efficacy in this patient population.

The clinical trial involves the use of **[18F]Fluor-PEG-Folate**, an experimental medication formulated as a **solution for injection**. This investigational product is administered via **intravenous infusion**. The active substance, **[18F]Fluoro-PEG-Folate**, is a polymer-based compound. The maximum daily dose is set at 203.5 MBq, with a total maximum dose of 407 MBq over a treatment period of up to 2 days. The administration schedule is designed to ensure optimal imaging results for the study's objectives, which focus on monitoring therapy response in patients with Rheumatoid Arthritis.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial's primary objective is to assess the association between changes in whole-body **[18F]PEG Folate PET/CT** imaging and clinical response to anti-TNF therapy in patients with established Rheumatoid Arthritis. The secondary objective is to correlate imaging outcomes with histological changes in synovial tissue, particularly focusing on macrophage infiltration and FRβ expression. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol and to maintain the integrity of the study data.

Efficacy in this clinical trial will be assessed by evaluating the association between quantitative changes in whole body **[18F]PEG Folate PET/CT** imaging after 4 weeks of anti-TNF therapy and the clinical response at 26 weeks in patients with established Rheumatoid Arthritis (RA). The primary endpoint is the correlation of these imaging changes with the clinical response to therapy, which will be monitored up to 26 weeks and considered the golden standard for assessment. The secondary objective involves relating the quantitative Folate PET outcomes after 4 weeks to histological changes in synovial tissue, with a focus on macrophage infiltration and FRβ expression. The efficacy parameters will be collected and analyzed at specified timepoints, particularly at 4 weeks and 26 weeks, using the Folate PET imaging technique. This approach aims to provide insights into the effectiveness of the PET tracer in visualizing and quantifying TNF expression in inflamed joints, thereby offering valuable data on its diagnostic potential in this patient population.