Japanese Phase 1 Study of Mepolizumab

Summary

SB-240563 is a fully humanized monoclonal antibody which is specific for human interleukin-5 (IL-5) and has been under development for severe refractory asthma. This study is the first study in Japanese subjects. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single dose SB-240563 administered intravenously to Japanese healthy male subjects.

Timeline

Start

2011-08-09

Primary completion

2012-04-27

Completion

2012-04-27

Publications

• Background Clutterbuck EJ, Hirst EM, Sanderson CJ. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood. 1989 May 1;73(6):1504-12.
• Background Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009 Mar 5;360(10):973-84. doi: 10.1056/NEJMoa0808991.
• Background Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, Bradley B, Durham SR, Collins JV, Jeffery PK, et al. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991 May;87(5):1541-6. doi: 10.1172/JCI115166.
• Background Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):704-8. doi: 10.1164/ajrccm.156.3.9610033.
• Background Robinson DS, Ying S, Bentley AM, Meng Q, North J, Durham SR, Kay AB, Hamid Q. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol. 1993 Sep;92(3):397-403. doi: 10.1016/0091-6749(93)90118-y.
• Background Smith DA, Minthorn EA, Beerahee M. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody. Clin Pharmacokinet. 2011 Apr;50(4):215-27. doi: 10.2165/11584340-000000000-00000.
• Background Wang JM, Rambaldi A, Biondi A, Chen ZG, Sanderson CJ, Mantovani A. Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol. 1989 Apr;19(4):701-5. doi: 10.1002/eji.1830190420.
• Background Wardlaw AJ, Brightling C, Green R, Woltmann G, Pavord I. Eosinophils in asthma and other allergic diseases. Br Med Bull. 2000;56(4):985-1003. doi: 10.1258/0007142001903490.

Drugs

Indications