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THU0191 Novel formulation of ct-p13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a phase i/iii randomised controlled trial
  1. R. Westhovens1,
  2. D.H. Yoo2,
  3. J. Jaworski3,
  4. E. Matyska-Piekarska3,
  5. S. Smiyan4,
  6. D. Ivanova5,
  7. A. Zielinska6,
  8. E.-K. Raussi7,
  9. A. Batalov8,
  10. S.J. Lee9,
  11. S.Y. Lee9,
  12. J.H. Suh9
  1. 1University Hospital KU Leuven, Leuven, Belgium
  2. 2Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of Ireland
  3. 3REUMATIKA – Centrum Reumatologii NZOZ, Warszawa, Poland
  4. 4State Higher Educational Institution “I. Ya. Horbachevskyi Ternopil State Medical University of MOH of Ukraine”, Ternopil, Ukraine
  5. 5Diagnostic-Consultative Center Aleksandrovska EOOD, Sofia, Bulgaria
  6. 6Medycyna Kliniczna, Warszawa, Poland
  7. 7North Estonia Medical Centre Foundation, Tallinn, Estonia
  8. 8Medical University – Plovdiv, University Hospital Kaspela, Clinic of Rheumatology, Plovdiv, Bulgaria
  9. 9Celltrion, Inc., Incheon, Korea, Republic of Ireland

Abstract

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

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.

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