THU0191 Novel formulation of ct-p13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a phase i/iii randomised controlled trial
Authors: R. Westhovens, D.H. Yoo, J. Jaworski, E. Matyska-Piekarska, S. Smiyan, D. Ivanova, A. Zielinska, E.-K. Raussi, A. Batalov, S.J. Lee, S.Y. Lee, J.H. Suh
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> While the treatment with intravenous (IV) CT-P13, an infliximab biosimilar, is effective and well tolerated, a new subcutaneous (SC) CT-P13 formulation (CT-P13 SC) is developed to provide additional, more convenient treatment options and opportunity for self-injection. <h3>Objectives</h3> To find the optimal dose of CT-P13 SC and to evaluate efficacy, PK and safety over the first 30 weeks in patients with rheumatoid arthritis. <h3>Methods</h3> This study consists of 1 cohort with CT-P13 IV, and 3 cohorts with 3 different doses of CT-P13 SC injected biweekly. All enrolled patients initially received CT-P13 IV at Weeks 0 and 2 and patients who received 2 full doses and displayed no safety concerns were randomly assigned to receive either CT-P13 SC or IV at Week 6. Using part 1 result, PK-PD modelling was conducted for the 3 regimens. <h3>Results</h3> A total of 50 patients were enrolled, of whom 48 patients were randomly assigned into 4 cohorts. Overall, the efficacy results of CT-P13 SC up to Week 30 were comparable to those of CT-P13 IV. Disease improvement by DAS28 and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (table 1). The safety profiles in CT-P13 SC cohorts were generally comparable to CT-P13 IV. One of the 2 patients who experienced a hypersensitivity reaction became anti-drug antibody (ADA) positive at Week 6 and experienced hypersensitivity from Week 2 to 8. All injection site reactions were grade 1 or 2. The proportion of ADA (positive) was lower in the SC cohorts. In PK-PD modelling, bioavailability was 59% (95% CI, 52%–67%). The dose linearity in SC regimens was confirmed based on Weeks 22 to 30 C<sub>trough</sub>, AUC<sub>τ</sub> and C<sub>max, ss</sub> (figure 1). C<sub>trough</sub> were greater (above 4 µg/mL) than the target exposure (1 µg/mL)<sup>[1][2]</sup> in all SC regimens. There was a trend towards slightly lower DAS28 score in all SC regimens, which was consistent with the higher C<sub>trough</sub> comparing with CT-P13 IV. Based on the exposure-response safety analyses, there was no correlation between PK (AUC<sub>τ</sub> or C<sub>max</sub>) and safety (IRRs or infections). Treatment continuation in patients enrolled with SB4 or oETN who were bionaive until enrollment. <h3>Conclusions</h3> CT-P13 SC showed comparable efficacy and safety with CT-P13 IV. The preliminary results suggest CT-P13 SC as a future alternative treatment of infliximab. <h3>References</h3> [1] Takeuchi, et al. 2009. [2] Mori, et al. 2007. <h3>Disclosure of Interest</h3> R. Westhovens Grant/research support from: Celltrion, Inc., BMS and Roche, Consultant for: Celltrion, Inc., Galapagos/Gilead and Janssen, D. H. Yoo Grant/research support from: Celltrion, Inc., J. Jaworski Grant/research support from: Celltrion, Inc., E. Matyska-Piekarska Grant/research support from: Celltrion, Inc., S. Smiyan Grant/research support from: Celltrion, Inc., D. Ivanova Grant/research support from: Celltrion, Inc., PPD, Quintiles, Egis Pharmaceuticals, and Pfizer., A. Zielinska Grant/research support from: Celltrion, Inc., E.-K. Raussi Grant/research support from: Celltrion, Inc. and Board of Estonian Society for Rheumatology, A. Batalov Grant/research support from: Celltrion, Inc., S. J. Lee Employee of: Celltrion, Inc., S. Y. Lee Employee of: Celltrion, Inc., J. H. Suh Employee of: Celltrion, Inc.