Tolerability, pharmacokinetics and pharmacodynamics of CMAB007, a humanized anti-immunoglobulin E monoclonal antibody, in healthy Chinese subjects.
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.
International Cancer Research Institute, The Second Military Medical University, Shanghai, China.
Bo
B
Zhou
Birong
B
Lin
Jing
J
Li
Weizhu
W
Qian
Sheng
S
Hou
Dapeng
D
Zhang
Geng
G
Kou
Bohua
B
Li
Hao
H
Wang
Yongchuan
Y
Chen
Yajun
Y
Guo
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D002681:China; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007279:Injections, Subcutaneous; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D007073:Immunoglobulin E