FRI0207 A phase I/II clinical trial of intra-articular administration of ARG098, an anti-FAS IGM monoclonal antibody, in knee joint synovitis of japanese patients with rheumatoid arthritis

Background ARG098, a chimeric anti-Fas IgM monoclonal antibody, possesses a novel mode of action totally different from those of currently available RA therapeutics including cytokine targeting biologics. The Fas molecule (also known as APO-1 or CD95) mediates apoptosis in response to Fas ligand (Fas-L). Preclinical studies demonstrated that ARG098 specifically targets the Fas molecule leads to apoptosis in synoviocytes. Objectives An open-label sequential dose-escalation study of ARG098 was conducted to assess the safety and efficacy. Methods 43 patients diagnosed by the ACR criteria with knee joint synovitis were enrolled. The study had 7 dose groups from 0.01, 0.03, 0.1, 0.3, 1, 3 and 10 μg/knee, 6 patients in each group (7 patients in 10 μg) and single dose of ARG098 was intra-articularly administered to the target knee. Patients were required to be hospitalized at least 4 days after administration for close safety monitoring, and the assessment continued for 8 weeks with visit bases. Results The results showed that ARG098 was well-tolerated and no serious adverse events were observed. Total 33 adverse events (AEs) in 19 patients, and drug-related AEs in 9 patients which included non-clinical hepatological and cardiological findings were confirmed, however those were occurred in low frequency and the severity was all mild. ARG098 serum concentration was below the limit of qualification level ( Conclusions The safety of single intra-articular administration of ARG098 was well-confirmed up to 10 μg/knee and the pain VAS assessment and MRI showed improvements. However the dose dependency was not clearly observed. Repeat administration of ARG098 Phase IIa placebo-controlled trial is ongoing to determine the appropriate dosage and assessment methods. Disclosure of Interest None Declared