Japanese Phase 1 Study of Mepolizumab

Asthma Clinical Trial

Official title: A Single Blind, Placebo Controlled, Parallel Group, Single Ascending Intravenous Dose Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SB-240563 (Mepolizumab) in Healthy Japanese Male Subjects.

Status Completed

Clinical Trial 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.

Clinical Trial Description

Asthma is a disease characterised by chronic airway inflammation, bronchial hyper-reactivity and variable airflow obstruction. Eosinophils are usually prominent in the airway inflammation seen in asthma and are considered a central cause in the pathogenesis of asthma. The expression of interleukin (IL)-5 is elevated in bronchoalveolar lavage (BAL) fluid and bronchial biopsies in patients with asthma. Moreover, the level of IL-5 in BAL fluid and the bronchial mucosa correlates with disease severity. The cytokine IL-5 promotes eosinophil differentiation, recruitment and survival. Thus a therapeutic strategy which blocks IL-5, thereby suppressing eosinophilic inflammation, may have therapeutic benefit in asthma.

SB-240563 (mepolizumab) is a humanized monoclonal antibody that blocks human interleukin 5 (hIL-5) from binding to its receptor. Initial clinical studies investigated the safety and efficacy of SB-240563 for the treatment of asthma and atopic dermatitis (AD). SB-240563 consistently and significantly reduced peripheral and tissue eosinophils in patients with these atopic conditions, including asthma, and in healthy volunteers.

SB-240563 is currently under development for severe refractory asthma and a Phase IIB dose-ranging study using the IV route of administration is currently ongoing. This study will be a single-blind, placebo-controlled, parallel group, dose ascending, single dose study in Japanese healthy male subjects.

Since this is the first study conducted in Japanese subjects, doses of SB-240563 will be administered in an ascending order. In studies conducted in non-Japanese subjects, SB-240563 has been well-tolerated following single and repeated intravenous dose up to 750 mg (SB-240563/006, SB-240563/036 and MEE103226). Intravenous repeated doses of 75 mg, 250 mg and 750 mg are being administered to non-Japanese asthma patients in an on-going Phase II study. In consideration of the above facts, single intravenous administration of 4 doses (10 mg, 75 mg, 250 mg and 750 mg) of SB-240563 will be administered in this study. A single intravenous dose of 10 mg will be administered in order to explore the effect of a lower dose of SB-240563 than previously studied on blood eosinophil counts. This low dose is expected to help further characterize the concentration-response relationship based on blood eosinophils.

This study is designed as a randomized, parallel group, placebo-controlled, single-blind study to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of SB-240563 in Japanese male subjects. ;

Related Conditions & MeSH terms

• Asthma

• NCT number: NCT01471327
• Study type: Interventional
• Source: GlaxoSmithKline
• Status: Completed
• Phase: Phase 1
• Start date: August 9, 2011
• Completion date: April 27, 2012