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P679 Development of a novel auto-injector of subcutaneous CT-P13 infliximab: Phase I randomised, open-label, single-dose trial to compare the pharmacokinetics and safety to pre-filled syringe in healthy subjects

S. Schreiber*1, S. Ben-Horin2, B. D. Ye3, R. Westhovens4, D. H. Yoo5, S. J. Lee6, J. H. Suh6, J. H. Byeon6, W. Reinisch7

1University Hospital Schleswig-Holstein, Kiel, Germany, 2Sheba Medical Center, Tel Hashomer, Israel, 3Asan Medical Center, Seoul, South Korea, 4University Hospital KU Leuven, Leuven, Belgium, 5Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 6Celltrion, Inc., Incheon, South Korea, 7Medical University Vienna, Vienna, Austria

Background

Comparable efficacy and safety were suggested between new subcutaneous (SC) and intravenous formulation of CT-P13 both in patients with rheumatoid arthritis1 and Crohn’s disease.2 As auto-injectors (AI) offer several advantages over pre-filled syringe (PFS) including simplified self-administration and reduced patient distress, CT-P13 SC AI is also being developed along with the CT-P13 SC PFS. This report is to demonstrate comparable pharmacokinetic (PK) and overall safety of CT-P13 SC administered by AI vs. PFS in healthy subjects.

Methods

Healthy subjects were enrolled and randomly assigned in a 1:1 ratio into one of the 2 arms (SC AI arm or SC PFS arm). In each arm, all subjects received a single dose of CT-P13 SC (120 mg) via AI or PFS on day 0, followed by 12 weeks during PK and safety were assessed. The primary endpoints were to demonstrate the bioequivalence of CT-P13 administration by AI vs. PFS defined by the confinement of the 90% CI of the geometric least squares means ratios of the primary PK parameters (AUC0-inf, AUC0-last, and Cmax) within the equivalence margin of 0.80 to 1.25.

Results

A total of 218 subjects (109 subjects in each arm) were randomised, and 215 subjects received study drug on day 0. In the PFS Group 3 subjects received no dose. Bioequivalence was established (Table 1). Overall, mean (±SD) serum concentration of CT-P13 following a single SC dose using AI or PFS showed similar trend throughout the study period (Figure 1). Safety results for CT-P13 SC AI were also comparable to those for SC PFS (Table 2). There were two cases of road accidents reported as serious adverse events and both were considered as unrelated to the study drug by the investigator. The proportion of subjects experienced injection site reaction was lower in SC AI compared with SC PFS, and the mean of injection site pain was also found to be lower than PFS. (6.7 and 9.0 scores for SC AI and SC PFS, 0 means no pain, 100 means extreme pain.) Generally, the proportion of subjects with positive anti-drug antibody results was similar between the CT-P13 SC AI and CT-P13 SC PFS arms during the study.

Conclusion

Equivalence of PK was demonstrated and comparable safety profiles were observed between healthy subjects treated with CT-P13 SC AI or PFS.

References

1. Westhovens R, Yoo DH, Jaworski J , et al. Novel formulation of CT-P13 for subcutaneous administration in patients with rheumatoid arthritis: initial results from a Phase I/III randomised controlled trial. Ann Rheum Dis 2018;77; abstract THU0191.

2. Schreiber, S, Jang B, Borzan V, et al. Novel formulation of CT-P13 (infliximab biosimilar) for subcutaneous administration: initial results from a phase I open-label randomised controlled trial in patients with active Crohn's disease. Gastroenterology 2018;154:S1371.