A Study of F8IL10 Intra-articular Treatment in Rheumatoid Arthritis

This protocol describes an open-label, non-randomized, ascending-dose Phase I study conducted in sequential cohorts of patients. The aim of the study is to assess the safety and tolerability of F8IL10 when administered via intra-articular (IA) route 3 times every 4 weeks in patients with RA. Eligible patients are male or female, ≥18 and ≤80 years old, with Rheumatoid Arthritis (RA) who, despite treatment with stable doses for at least 3 months of DMARDs (conventional, biologic and/or targeted synthetic), present arthritis flare(s) suitable for IA injection in a knee, shoulder, ankle, wrist or elbow. The study will take place in two stages: 1. The dose-escalation part is designed with an accelerated phase, followed by a classical 3+3 dose-escalation scheme. Patients will be sequentially assigned to the following F8IL10 concentration levels: * Cohort 1: 0.05 µg/mL * Cohort 2: 0.5 µg/mL * Cohort 3: 5 µg/mL * Cohort 4: 20 µg/mL * Cohort 5: 50 µg/mL * Cohort 6: 100 µg/mL * Cohort 7: 150 µg/mL * Cohort 8: 200 µg/mL The administered volume depends on the target joint: 5 mL for knee, 4 mL for shoulder, 2 mL for ankle or elbow, and 1 mL for wrist. Therefore, the actual administered dose varies according to both the cohort concentration and the joint treated. 2. Following successful identification of the RD, the study will proceed with a dose-expansion part, during which 12 patients will be treated at the RD concentration level, including those already treated at that level during dose escalation. Patients will receive intra-articular administrations of F8IL10 every 4 weeks for up to 3 administrations, at Week 1, Week 5 and Week 9. Following completion of treatment, patients will continue with Follow-up every 4 weeks from Week 13, or End of Treatment, up to Week 37, to monitor safety, treatment response and any need to introduce or modify DMARD therapy. The primary objective is to evaluate the safety of F8IL10 when administered by IA injection and to determine the maximum tolerated dose (MTD) in order to establish the recommended dose (RD). MTD, RD and maximum administered dose (MAD) are defined as joint-independent F8IL10 concentrations applicable across all evaluated joint types. Secondary objectives are to assess early signs of efficacy and to determine the pharmacokinetic profile and immunogenicity of intra-articular F8IL10