Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma (DREAM)

Inclusion Criteria:

• Male or female
• Aged 12 to 65 years inclusive
• Minimum weight 45kg
• Clinical features of severe refractory asthma
• Well documented requirement for high dose inhaled corticosteroids (ICS) [i.e. >= 880mcg/day fluticasone propionate or equivalent daily] for at least 12 months
• Using additional controller medication in addition to high dose ICS for at least 12 months
• Persistent airflow obstruction indicated by a pre-bronchodilator FEV1<80% predicted at visit 1 or 2 or peak flow diurnal variability of >20% on 3 or more days during the run-in
• Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (>=300/microL), sputum eosinophils (>=3%), exhaled nitric oxide (>=50ppb) or prompt deterioration of asthma control following a <=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)
• History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months
• Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability
• ECG assessment demonstrating QTc<450msec or QTc<480msec for patients with bundle branch block
• Liver function tests demonstrating ALT<2xUpper Limit of Normal (ULN), AST<2xULN, Alk Phos <=1.5xULN, bilirubin <=1.5xULN
• Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception
• Able to give written informed consent
• Able to read, comprehend and write at a sufficient level to complete study materials

Exclusion Criteria:

• Current smokers or smoking history of >=10 pack years
• Clinically important lung condition other than asthma
• Diagnosis of malignancy or in the process of investigation
• Unstable liver disease
• Churg-Strauss syndrome
• Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening
• Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1
• Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months
• Allergy/intolerance to the excipients in the mepolizumab formulation
• Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer
• Pregnant or breastfeeding or planning to become pregnant
• Clinically significant disease which is uncontrolled with standard treatment
• History of alcohol misuse or substance abuse
• Parasitic infestation within previous 6 months
• Known immunodeficiency
• Unable to follow instructions, use the electronic diary or peak flow meter
• Known evidence of lack of adherence to controller medications and/or follow physician's recommendations
• Previous participation in a study of mepolizumab and received study medication within 90 days