Conditions: Asthma
Keywords: Dose-ranging Safety Pharmacodynamics eosinophils SB-240563 Efficacy Severe refractory asthma mepolizumab Placebo
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 621
Healthy volunteers: no

Brief summary:
The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.

Detailed description:
A double-blind, placebo-controlled study to evaluate the efficacy, safety and pharmacodynamics of three doses (75 mg, 250 mg and 750 mg) of mepolizumab intravenous (i.v.) administered every 4 weeks compared with placebo over a 52-week treatment period in subjects with severe uncontrolled refractory asthma. Efficacy will be measured by the frequency of asthma exacerbations. In addition lung function, rescue medication usage, daily symptoms, asthma control score, asthma quality of life score and withdrawals due to asthma exacerbations will be assessed. Safety will be assessed by adverse events, clinical laboratory evaluations, ECGs, immunogenicity and vital signs. Pharmacodynamics will be assessed by eosinophil levels in blood, serum IL-5 and eosinophil levels in induced sputum.

Arms:
arm 1: Mepolizumab 750mcg i.v. every 4 weeks arm 2: Mepolizumab 250mcg i.v. every 4 weeks arm 3: Mepolizumab 75mcg i.v. every 4 weeks arm 4: Placebo saline every 4 weeks i.v.

Interventions: intervention 1: Mepolizumab 750 intervention 2: Mepolizumab 250 intervention 3: Mepolizumab 75 intervention 4: Placebo saline
Intervention descriptions: intervention 1: Mepolizumab 750mg every four weeks by i.v. intervention 2: Mepolizumab 250mg every four weeks by i.v. intervention 3: Mepolizumab 75mg every four weeks by i.v. intervention 4: Placebo saline every four weeks by i.v.

Protocol document: