Tolerability, pharmacokinetics and pharmacodynamics of CMAB007, a humanized anti-immunoglobulin E monoclonal antibody, in healthy Chinese subjects

Abstract

The goal of the studies presented here was to determine the tolerability, pharmacokinetic and pharmacodynamic profiles of CMAB007, a biosimilar of omalizumab (Xolair; a humanized anti-immunoglobulin E monoclonal antibody), in healthy, male Chinese subjects. Thirty-six healthy Chinese men participated in two open-label, dose-escalation studies: 27 in a single-dose study (150, 300 or 600 mg) and 9 in a multiple-dose study (150 or 300 mg every 4 weeks for 20 weeks). The safety profiles of both studies were generally unremarkable. No drug-related adverse event was observed. CMAB007 exhibited a linear PK profile over the dose range of 150–600 mg. In the single-dose study, maximum concentration (Cmax) was reached within 6–8 d, and Cmax and area under concentration-time curve (AUC) increased linearly with the dose. In the multiple-dose study, steady-state appeared to have been achieved after the third dose. Css-max and AUCτ also showed dose-linearity. A dose-dependent suppression of free IgE was observed during treatment, as a median percentage change from baseline, 91.9–98.8%, in the three single-dose groups. No anti-CMAB007 antibodies were detected after dosing in any subject. Subcutaneous administration of CMAB007 was well-tolerated and seemed to be effective in reducing free IgE in healthy Chinese volunteers, which provides important information for further clinical studies.

Key words:

• pharmacokinetics
• pharmacodynamics
• safety
• IgE
• humanized antibody

Acknowledgments

This work was supported by grants from National Natural Science Foundation of China, Ministry of Science and Technology of China (973 and 863 program projects), State Key Project for New Drug Development and Infectious Diseases and Shanghai Commission of Science and Technology (Key Laboratory and Projects).

Figures and Tables

Figure 1 Serum CMAB007 concentration-time curve in healthy, male Chinese subjects after single SC administration of different doses. CMAB007 150 mg (□); CMAB007 300 mg (●); CMAB007 600 mg (△) (n = 9 for each dose group). Data were expressed as mean ± SD.

Figure 2 Linear regression analyses of (A) AUC_0-∞ (R², 0.9997) and (B) C_max (R², 0.9979) of CMAB007 after single SC administration. Individual value (○).

Figure 3 Serum CMAB007 concentration-time curve in healthy, male Chinese subjects following multiple SC doses of 150 mg q4wk × 6 (□, n = 3) and 300 mg q4wk × 6 (●, n = 5). Data were expressed as mean ± SD.

Figure 4 Serum CMAB007 concentration-time curve in healthy, male Chinese subjects following single and multiple doses of 150 mg and 300 mg. Single-dose of 150 mg (○, n = 9); multiple-dose of 150 mg (●, n = 3); single-dose of 300 mg (△, n = 9); multiple-dose of 300 mg (▴, n = 5). Data were expressed as mean values.

Figure 5 Serum concentration-time curve of (A) total IgE and (B) free IgE after single SC administration of different doses. CMAB007 150 mg (□); CMAB007 300 mg (●); CMAB007 600 mg (△) (n = 9 for each dose group). Data were expressed as mean ± SD.

Table 1 Demographic characteristics of subjects enrolled in single- and multiple-dose studies

Table 2 Treatment-emergent adverse events reported during single- and multiple-dose administration of CMAB007

Table 3 Noncompartmental and one-compartmental pharmacokinetic parameters of CMAB007 after administration of single doses in healthy Chinese subjects

Table 4 Noncompartmental and one-compartmental of individual pharmacokinetic parameters of CMAB007 at steady-state in healthy Chinese subjects

Table 5 PK/PD of CMAB007 vs. Xolair^®