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.

Elegible patients of this trial are male or female, ≥ 18 and ≤ 80 years old, patients 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 of the study is designed with an accelerated phase, followed by a classical 3+3 dose escalation scheme. Patients will be sequentially assigned to the following dose levels:

* Cohort 1: 25 μg F8IL10 * Cohort 2: 50 μg F8IL10 * Cohort 3: 100 μg F8IL10 * Cohort 4: 400 μg F8IL10 * Cohort 5: 700 μg F8IL10 * Cohort 6: 1000 μg F8IL10 2. Following successful identification of the RD, the study will proceed with a dose expansion part, during which 12 patients will be treated at RD (including those treated in the dose escalation part).

Patients will receive intra-articular administations of F8IL10 every 4 weeks for up to 3 administrations.

Following completion of the treatment, patients will continue with Follow-up for up to 6 months (Week 37) to monitor the duration of treatment response as well as their health status, the possible onset of post-treatment AEs and the modifications to the treatment that may be required to manage disease symptoms, if any.

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).

Secondary objectives are to assess early signs of efficacy and to determine the pharmacokinetic profile and immunogenicity of intra-articular F8IL10.