Japanese Phase 1 Study of Mepolizumab
Condition: Asthma
Study type: Interventional
Phase: Phase 1

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.
    

Detailed 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.
    

Intervention name(s): SB-240563; Placebo
Intervention type(s): Biological; Other
Intervention description(s): 10mg, 75mg, 250mg and 750mg IV, single dose on Day 1; Saline IV, single dose at Day 1
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Other