TY - JOUR T1 - Safety, Tolerability, and Clinical Outcomes after Intraarticular Injection of a Recombinant Adeno-associated Vector Containing a Tumor Necrosis Factor Antagonist Gene: Results of a Phase 1/2 Study JF - The Journal of Rheumatology JO - J Rheumatol SP - 692 LP - 703 DO - 10.3899/jrheum.090817 VL - 37 IS - 4 AU - PHILIP J. MEASE AU - NATHAN WEI AU - EDWARD J. FUDMAN AU - ALAN J. KIVITZ AU - JOY SCHECHTMAN AU - ROBERT G. TRAPP AU - KATHRYN F. HOBBS AU - MARIA GREENWALD AU - ANTONY HOU AU - STEPHEN A. BOOKBINDER AU - GALEN E. GRAHAM AU - CRAIG W. WIESENHUTTER AU - LARRY WILLIS AU - ERIC M. RUDERMAN AU - JOSEPH Z. FORSTOT AU - MICHAEL J. MARICIC AU - KATHRYN H. DAO AU - CHARLES H. PRITCHARD AU - DARRELL N. FISKE AU - FRANCIS X. BURCH AU - H. MALIN PRUPAS AU - PERVIN ANKLESARIA AU - ALISON E. HEALD Y1 - 2010/04/01 UR - http://www.jrheum.org/content/37/4/692.abstract N2 - Objective. To assess safety and clinical outcomes in patients with inflammatory arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant adeno-associated viral vector containing the human tumor necrosis factor (TNF) receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. Methods. In this phase 1/2 randomized study, adults with persistent moderate or severe inflammation in a target joint, being treated with or without systemic anti-TNF therapy, received a single IA injection of either rAAV2-TNFR:Fc (1 × 1011, 1 × 1012, or 1 × 1013 DNase-resistant particles/ml joint volume) or placebo, followed by open-label rAAV2-TNFR:Fc 12–30 weeks later, depending on when the target joint met predetermined criteria for reinjection. Results. 127 subjects received the first injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc. Administration site reactions, consisting of transient mild to moderate increases in tenderness and swelling of the injected joint, occurred after 23/191 (12%) rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events were not dose-dependent. Notable serious adverse events (SAE) included culture-negative septic arthritis in a subject receiving leflunomide and fatal disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p = 0.14). Conclusion. IA rAAV2-TNFR:Fc resulted in administration site reactions after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered not related to study agent. Patient-reported outcome measures of clinical response showed greater improvement in treated patients than placebo patients. ER -