Background/Purpose CT-P13 has been approved as the first biosimilar to innovator infliximab sourced from European Union (EU‑INX) in Sep 2013. Even if it has been concluded as equivalent or comparable to EU‑INX through pivotal studies and switching studies, it was questioned about the comparability between reference products with different origins^1,2,3,4.

This study was designed to demonstrate comparability among CT‑P13, EU-INX and US-sourced infliximab (US-INX) in healthy volunteers and to examine whether three-biologic infliximab from the different manufacturing sources are comparable to each other primarily in pharmacokinetics (PK).

Methods In this double blind, randomized, parallel group, single-dose study, a total of 213 healthy volunteers were randomized 1:1:1 to receive a single dose (5 mg/kg) of CT‑P13, EU-INX or US-INX by intravenous infusion on Day 1 followed for 8 weeks. The primary endpoints were maximum serum concentration (C_max), area under the concentration-time curve from time zero to the last quantifiable concentration (AUC_last) and area under the concentration-time curve from time zero to infinity (AUC_inf) of CT-P13, EU-INX and US-INX. A total of 11 serum blood samples were obtained for the primary PK analysis, and safety and tolerability were also evaluated up to 8 weeks. Similarity of systemic exposure (C_max, AUC_last and AUC_inf) was considered to be demonstrated if the 90% confidence interval (CI) for the ratio of geometric means was within the acceptance interval of 0.8 to 1.25 for the following comparisons: CT-P13 vs EU-INX, CT-P13 vs US-INX, and EU-INX vs US-INX.

Results The baseline demographics for 213 subjects among 3 study groups were highly similar. The PK parameters in the study groups were highly similar (Table 1). The 90% CI for the ratios of C_max, AUC_last and AUC_inf were within the acceptance interval of 0.8 to 1.25 for the comparisons of CT-P13 to EU-INX, CT-P13 to US-INX and EU-INX to US-INX.

Adverse events (AEs) were similar between 3 study groups with AEs related to the study drug reported by 39.4%, 23.9%, and 42.3% of subjects in CT-P13, EU-INX and US-INX groups, respectively. The majority of AEs related to the study drug reported in the study groups was Grade 1, and there was only 1 AE reported as Grade 3 in US-INX group based on Common Terminology Criteria for Adverse Events. No serious AE related to the study drug was reported, and no AEs led to the withdrawal of a subject from the study. All AEs related to study drug were resolved by the end of the study.

Table 1. Pharmacokinetic Exposure Estimates (Mean ± SD)

Parameters (units)	CT-P13 (N=71)	EU-INX (N=71)	US-INX (N=71)
Cmax (ug/mL)	127.6 ± 21.6	121.3 ± 19.7	119.9 ± 19.5
AUClast (h*ug/mL)	31343.2 ± 7107.3	30669.0 ± 6020.5	31629.6 ± 5886.8
AUCinf (h*ug/mL)	33212.3 ± 8326.1	32986.6 ± 7806.8	34363.6 ± 8004.2

Conclusion Equivalence of PK in terms of C_max, AUC_last and AUC_infwas demonstrated and comparable safety profiles were observed in the comparisons of CT-P13 to EU-INX, CT-P13 to US-INX and EU-INX to US-INX in healthy volunteers.

 References

1. Park W, et al. Ann Rheum Dis 2013;72:1605-12
2. Yoo DH, et al. Ann Rheum Dis 2013;72:1613-20
3. Yoo DH, et al. Arthritis Rheum 2013;65(12): 3319
4. Park W, et al. Arthritis Rheum 2013;65(12): 3323

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-three-arm-parallel-group-single-dose-study-to-compare-the-pharmacokinetics-safety-and-tolerability-of-three-formulations-of-infliximab-ct-p13-eu-sourced-infliximab-an/