Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Emicizumab in Healthy Chinese Subjects

• Published in: Clinical pharmacology in drug development Vol. 10; no. 1; pp. 30 - 38
• Main Authors: Li, Haiyan, Zhang, Weijiang, Petry, Claire, Li, Lindong, Fernandez, Elena, Kiialainen, Anna, Feng, Sheng, Hsu, Wanling, Li, Li, Wei, Yudong, Schmitt, Christophe
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2021; John Wiley and Sons Inc
• Subjects: Adult; Antibodies - blood; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - blood; Antibodies, Bispecific - pharmacokinetics; Antibodies, Bispecific - pharmacology; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - blood; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - pharmacology; Asians; Chinese; emicizumab; Factor VIII - analysis; healthy subjects; Healthy Volunteers; Humans; Injections, Subcutaneous; Male; Monoclonal antibodies; Original Manuscript; Pharmacodynamics; Pharmacokinetics; Whites; Young Adult; emicizumab; pharmacokinetics; Chinese; healthy subjects; pharmacodynamics
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.805

This phase 1, open‐label, single‐center study evaluated the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of single‐dose emicizumab in healthy Chinese males. Overall, 16 subjects received a single subcutaneous dose of 1‐mg/kg emicizumab. Blood samples were obtained before dosing on day 1 and at regular intervals over 16 weeks after dosing for PK evaluation. A single 1‐mg/kg subcutaneous dose of emicizumab was safe and well tolerated in healthy Chinese male subjects in the study. Mean (± standard deviation) area under the concentration‐time curve from time 0 to infinity and maximum concentration were 287 ± 74.2 μg⋅d/mL and 7.11 ± 1.77 μg/mL, respectively, with a terminal half‐life of 26.7 (±4.3) days. Emicizumab administration did not show significant impact on pharmacodynamic markers tested, which mostly remained stable throughout the study. One subject tested positive for antidrug antibody, with no impact on his PK or safety profile. Compared with results from healthy Japanese and Caucasian subjects receiving the same dose in previous clinical trials, the current results further indicated the absence of difference of emicizumab PK profile across Chinese, Japanese, and Caucasian subjects, validating the use of similar therapeutic doses in Asian and non‐Asian populations.