Safety, tolerability and pharmacokinetics of a human anti-interleukin-13 monoclonal antibody (CNTO 5825) in an ascending single-dose first-in-human study
Article first published online: 8 APR 2013
© 2012 Janssen Research & Development, LLC. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 5, pages 1289–1298, May 2013
How to Cite
van Hartingsveldt, B., Nnane, I. P., Bouman-Thio, E., Loza, M. J., Piantone, A., Davis, H. M. and Petty, K. J. (2013), Safety, tolerability and pharmacokinetics of a human anti-interleukin-13 monoclonal antibody (CNTO 5825) in an ascending single-dose first-in-human study. British Journal of Clinical Pharmacology, 75: 1289–1298. doi: 10.1111/j.1365-2125.2012.04477.x
- Issue published online: 8 APR 2013
- Article first published online: 8 APR 2013
- Accepted manuscript online: 8 OCT 2012 09:30AM EST
- Manuscript Accepted: 20 SEP 2012
- Manuscript Received: 13 JUN 2012
- first-in-human study;
- monoclonal antibody;
To assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of CNTO 5825 following single-dose intravenous (i.v.) and subcutaneous (s.c.) administration in healthy and healthy atopic subjects.
Sixty-four subjects received a single dose of placebo or CNTO 5825 (0.1, 0.3, 1.0, 3.0, or 10 mg kg−1 i.v. in a dose-escalating manner, or 3.0 mg kg−1 s.c. in healthy subjects; and 10 mg kg−1 i.v. in healthy atopic subjects). Subjects were observed for 96 h postadministration and followed for 16 weeks. Safety and tolerability were monitored, and serum samples were collected to measure CNTO 5825 concentrations, antibodies to CNTO 5825 and PD biomarkers.
Most adverse events were mild to moderate in severity and considered to be unrelated to CNTO 5825, with no dose-dependent trends seen. The two serious adverse events were considered to be unrelated to CNTO 5825. After i.v. administration, CNTO 5825 exhibited linear PK, with a terminal half-life of ∼22–32 days. After a single 3 mg kg−1 s.c. dose in healthy subjects, CNTO 5825 was absorbed into the systemic circulation with a median time to maximum serum concentration (tmax) of 5.45 days and absolute bioavailability of ∼75%. The PK profile of CNTO 5825 at 10 mg kg−1 was similar in both healthy and healthy atopic subjects. No antibodies to CNTO 5825 were detected through week 16. In the CNTO 5825-treated healthy atopic subjects, there was a significant reduction in serum IgE and C-C motif chemokine ligand 17 (P = 0.028 and 0.068 vs. placebo, respectively).
CNTO 5825 was well tolerated, had an acceptable safety profile, exhibited linear PK characteristics, and no detected antibodies to CNTO 5825.