A Safety and Efficacy Study of Mepolizumab in Subjects With Severe Asthma

Inclusion Criteria

• Subjects who will be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
• Subjects with at least 12 years of age at Visit 0 and a minimum weight of 40 kilograms.
• Persistent airflow obstruction as indicated by: For subjects >=18 years of age at visit 1, a pre-bronchodilator FEV1 =300 cells per microliters that is related to asthma in the past 12 months prior to Visit 1 or a peripheral blood eosinophil count of >=150 cells per microliters at Visit 1 that is related to asthma).
• Regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1, of which at least 9 months accumulated documented is required, the 3 months prior to Visit 1 is mandatory. With or without maintenance oral corticosteroids (OCS). ICS dose must be >=500 microgram per day fluticasone propionate (FP) or equivalent daily (for ICS/long-acting beta-2-agonists combination preparations, Seretide 50/250 micrograms twice daily and above or equivalent will meet this ICS criteria). (Maintenance OCS is defined as a prescribed regimen of a minimum average daily dose of prednisone 5 milligrams [or equivalent]).
• Current treatment with an additional controller medication, besides ICS, for at least 3 months. (Example given [e.g.], long-acting beta-2-agonist, leukotriene receptor antagonist [LTRA], or theophylline).
• Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroid (intramuscular [IM], intravenous, or oral), in the 12 months prior to Visit 1, despite the use of high-dose ICS. For subjects receiving maintenance corticosteroid, the corticosteroid treatment for the exacerbations must have been a two-fold increase or greater in the dose for at least 3 days is required.
• A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of =10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a subject who quit smoking at least 6 months prior to Visit 1.
• Presence of a known pre-existing, clinically significant lung condition other than asthma, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study. This includes current bacterial or viral infection of the upper or lower respiratory tract, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer. Clinically Significant is defined as any disease/condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
• A chest X-ray that reveals evidence of clinically significant abnormalities not believed to be due to the presence of asthma.
• Bronchial Thermoplasty and Radiotherapy are excluded for 12 months prior to visit 1 and throughout the study.
• A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).
• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or cirrhosis. Subjects with ALT >2 times Upper Limit