THU0191 Novel formulation of ct-p13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a phase i/iii randomised controlled trial

Background 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. Objectives 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. Methods 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. Results 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 Ctrough, AUCτ and Cmax, ss (figure 1). Ctrough were greater (above 4 µg/mL) than the target exposure (1 µg/mL)[1][2] in all SC regimens. There was a trend towards slightly lower DAS28 score in all SC regimens, which was consistent with the higher Ctrough comparing with CT-P13 IV. Based on the exposure-response safety analyses, there was no correlation between PK (AUCτ or Cmax) and safety (IRRs or infections). Abstract THU0191 – Table 1 Efficacy and safety up to Week 30 Cohort 1IV 3 mg/kg(n=13) Cohort 2SC 90 mg(n=11) Cohort 3SC 120 mg(n=12) Cohort 4SC 180 mg(n=12) DAS28 (CRP), mean±SD Week 0 5.4±0.8 6.3±0.8 5.7±0.9 5.5±0.8 Week 6 3.9±1.5 4.6±1.1 3.9±1.2 3.4±1.2 Week 22 3.9±1.6 3.7±1.0 3.3±1.4 2.8±1.3 Week 30 3.3±1.3 3.0±1.1 3.1±1.0 2.7±1.0 ACR20,n (%) Week 6 8 (61.5) 8 (72.7) 7 (58.3) 7 (58.3) Week 22 8 (61.5) 8 (72.7) 9 (75.0) 11 (91.7) Week 30 11 (84.6) 10 (90.9) 10 (83.3) 12 (100) Safety, n (%) Hypersensitivity/IRR 0 1 (9.1) 1 (8.3) 0 Injection site reactions 0 2 (18.2) 0 2 (16.7) Infections 4 (30.8) 2 (18.2) 0 4 (33.3) ADA 9 (69.2) 3 (27.3) 4 (33.3) 1 (8.3)Abstract THU0191 – Figure 1 Mean (± SD) Simulated CT-P13 Serum Concentration vs Time Profiles for the Simulated Fixed Dose SC Maintenance Dosing Regimens with Overlaid IV Maintenance Reference Treatment (Semi-Logarithmic Scale). Solid line=Period 1 (IV reference regimen: IV loading+IV maintenance dose). Dashed line=Period 2 (SC test regimen: IV loading+SC maintenance dose)Abstract THU0191 – Table 2 Summary of Steady State Median (Prediction Interval 5th-95th percentile) CT-P13 Exposure Results Treatment continuation in patients enrolled with SB4 or oETN who were bionaive until enrollment. Conclusions 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. References [1] Takeuchi, et al. 2009. [2] Mori, et al. 2007. Disclosure of Interest 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.