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

Exclusion Criteria

• •Current smokers or former smokers with a smoking history 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 of Normal (ULN), bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent)
• •Subjects who have known, pre-existing severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: known ejection fraction of \<30 percent or severe heart failure meeting New York Heart Association Class IV classification or hospitalized in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III or angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.
• •QT interval corrected by Fridericia's formula (QTc\[F\]) \>450 milliseconds (msec) or QTc(F) \>480 msec for subjects with Bundle Branch Block at Visit 1 is exclusive.
• •Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment. Current malignancy except for basal and squamous skin cancer.
• •Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophagitis.
• •Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also excluded.
• •A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1. Alcohol abuse is defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than three units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than two units (females). One unit was equivalent to a half-pint (220 milliliters) of beer or one (25 milliliters) measure of spirits or one glass (125 milliliters) of wine.
• •A known immunodeficiency (e.g., human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
• •Subjects who have received omalizumab (Xolair) within 130 days of Visit 1.
• •Subjects who have received any monoclonal antibodies (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
• •Use of herbals within 7 days prior to visit 1, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• •Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to visit 1 (this also includes investigational formulations of marketed products).
• •Subjects with allergy/intolerance to a monoclonal antibody or biologic.
• •Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
• •Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
• •Previously participated in any study with mepolizumab and received investigational product (including placebo).
• •A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
• •Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. Re-screening of subjects will be allowed only upon approval by the medical monitor.