Background Our approach allows the selective delivery and accumulation of IL-10 at sites of inflammation [1,2], using DEKAVIL, an “armed antibody”, composed of the human F8 antibody fragment (specific to the EDA domain of fibronectin) fused to the immunoregulatory cytokine IL-10. This represents a novel therapeutic concept for treatment of chronic inflammation. A potent inhibition of arthritis progression has previously been reported in a model of arthritis [1,2] using DEKAVIL or a murine analogue in combination with MTX. A Phase Ib clinical trial is on-going, featuring weekly administation of DEKAVIL in combination with MTX, to patients with active RA who have failed at least one line of anti-TNF therapy. We now report the results obtained within the first six dose levels.
Objectives To establish the MTD of the combined treatment, Dekavil + methotrexate. To study safety and tolerability. To obtain preliminary information on efficacy.
Methods Cohorts of 3-4 patients with active RA received escalating doses of DEKAVIL (6, 15, 30, 60, 110 and 160 μg/kg respectively) in combination with fixed dose of MTX (10-15 mg/week). The treatment was given as once weekly sc injection for up to 8 weeks. Safety evaluations based on RCTC v.2.0  on days 1 through 28, including AEs, SAEs and tests were used to determine the DLT, if any. Response was assessed after 4 and 8 weeks of treatment, according to ACR and DAS28 criteria
Results Twenty patients have been treated and were evaluable for safety from dose levels between 6 and 160 μg/kg. No MTD has been reached. No DLTs have been encountered or SAEs recorded. Reported adverse reactions were several mild injection site reactions and a single reported systemic adverse reaction, a progressive anaemia at the highest dose level tested so far. Treatment was witheld and the event resolved within 3 weeks. Considering the maximum ACR response achieved: three patients achieved an ACR 70 response, three patients achieved an ACR 50 response and six patients achieved an ACR20 response at various time points during regular or extended follow-up. Variation in the duration of the response has been observed. Of note stand out two patients in the 30 μg/kg cohort and in the 60 μg/kg cohort who achieved long-lasting remission: ACR70s at week 60 (Patient 8) and week 44 (Patient 11), still on-going. A low-titer of anti-fusion protein antibodies was reported for two out of fifteen samples analyzed.
Conclusions The promising safety data on the clinical use of DEKAVIL in combination with MTX together with the preliminary positive signs of anti-arthritic activity suggest that the targeted delivery of IL-10 to the site of inflammation may be beneficial to patients with RA. The extended activity periods indicate the possibility for a long lasting therapeutic potential. These results warrant further clinical investigation in the future in randomized trials.
K. Schwager et al. (2009) Arthritis Res. Ther., 11, R142.
F. Doll et al (2013) Arthritis Res. Ther., 15, R138.
T. Woodworth et al. (2007) J. Rheumatol., 34: 1401-14.
Disclosure of Interest M. Galeazzi: None declared, L. Bazzichi: None declared, G. Sebastiani: None declared, D. Neri Shareholder of: Philogen, L. Giovannoni Employee of: Philogen, F. Bacchion Employee of: Philogen, J. Wilton Consultant for: Philogen, E. Garcia Gonzalez Employee of: Philogen, P. Ruffini Employee of: Dompé, M. Bardelli: None declared, C. Baldi: None declared, E. Selvi: None declared, G. Minisola: None declared, R. Caporali: None declared, E. Prisco: None declared, S. Bombardieri: None declared