Background/Purpose: CT-P17 was developed as the first biosimilar of the high concentration (100 mg/mL), citrate-free formulation of reference adalimumab. The purpose of this study was to compare the pharmacokinetics (PK), safety, and immunogenicity of CT-P17 to EU-approved adalimumab (EU-adalimumab) and US-licensed adalimumab (US-adalimumab) up to Day 71 after a single subcutaneous (SC) injection of 40 mg (100 mg/mL) of each product in healthy subjects.

Methods: 312 healthy subjects aged 19 to 55 years were randomly assigned 1:1:1 to receive either CT-P17, EU-adalimumab or US-adalimumab. The primary objective was to evaluate PK equivalence based on area under the concentration-time curve (AUC) from time zero to infinity (AUC_0-inf), AUC from time zero to the last quantifiable concentration (AUC_0-last), and maximum serum concentration (C_max). Secondary objectives were to assess additional PK parameters, safety, and immunogenicity.

Results: Demographics and baseline characteristics were well balanced among the 3 treatment groups. The 90% confidence intervals (CI) for the geometric least squares mean ratios of each of the primary PK parameters (AUC_0–inf, AUC_0–last, and C_max) were within the predefined equivalence margin of 80% to 125% (Table 1). Secondary PK parameters (T_max, t_1/2, λ_z, CL/F, V_z/F, and %AUC_extrap) were similar among the 3 treatment groups. Mean serum concentrations of adalimumab to Day 71 were comparable among the 3 treatment groups (Figure 1).

The overall safety profile was comparable among the 3 treatment groups (Table 2). The most frequently reported treatment-emergent adverse event (TEAE) was injection site reaction. Overall, most TEAEs were Grade 1 or 2 in intensity. There were 3 treatment-emergent serious adverse events (TESAEs), each of which was assessed as being unrelated to study drug.

Similar numbers of subjects among the 3 treatment groups tested positive for anti-drug antibodies (ADA) and neutralizing ADA (NAb). Overall, 99 (97.1%), 96 (94.1%) and 99 (95.2%) subjects in the CT-P17, US-adalimumab and EU-adalimumab groups, respectively, had ≥1 positive ADA result post-treatment and 79 (77.5%), 85 (83.3%) and 84 (80.8%) subjects in the CT-P17, US-adalimumab and EU-adalimumab groups, respectively, had ≥1 positive NAb result post-treatment. ADA titers were similar across the 3 treatment groups. AUC_0–inf and AUC_0–last each correlated negatively with ADA titer in all treatment groups (P-value < 0.0001; calculated using Fisher's z transformation). There was no statistically significant correlation of C_max with ADA titer.

Conclusion: This study demonstrated PK equivalence of CT-P17 to the high concentration (100 mg/mL), citrate-free formulation of both US- and EU-sourced reference adalimumab in healthy subjects. Safety profiles, including immunogenicity, were comparable among the 3 treatment groups.

Abbreviations: AUC0–inf, area under the concentration–time curve from time zero to infinity; AUC0–last, area under the concentration–time curve from time zero to the last quantifiable concentration; CI, confidence interval; Cmax, maximum serum concentration; EU adalimumab, European Union-approved adalimumab; gLSM, geometric least squares mean; US-adalimumab, United States-licensed adalimumab. *Ratio of geometric least squares mean and 90% CIs for the ratios

Abbreviations: EU-adalimumab, European Union-approved adalimumab; SD, standard deviation; US-adalimumab, United States-licensed adalimumab.

Abbreviations: EU-adalimumab = European Union-approved adalimumab; TEAE = treatment-emergent adverse event; TESAE = treatment-emergent serious adverse event; US-adalimumab = United States-licensed adalimumab.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetics-and-safety-of-ct-p17-a-proposed-high-concentration-100-mg-ml-adalimumab-biosimilar-in-comparison-with-eu-approved-adalimumab-and-us-licensed-adalimumab-results-of-a-phase-1-rand/