Mepolizumab in Chronic Obstructive Pulmonary Diseases (COPD) With Eosinophilic Bronchitis

Inclusion Criteria:

• Diagnosis: An established clinical history of COPD in accordance with the definitionby the American Thoracic Society/European Respiratory Society as follows: Chronicobstructive pulmonary disease is a preventable and treatable disease statecharacterized by airflow limitation that is not fully reversible. The airflowlimitation is usually progressive and is associated with an abnormal inflammatoryresponse of the lungs to noxious particles or gases, primarily caused by cigarettesmoking. Although COPD affects the lungs, it also produces significant systemicconsequences

• Sputum eosinophils > 3% at randomization and on at least one occasion in the past 2years. If this historic data is not available, documented improvement in Forcedexpired volume in 1 second (FEV1) of at least 12% with a course of prednisone in thepast 2 years will be used as a surrogate for the presence of airway eosinophilia

• FEV1/Vital Capacity (VC) < 70% and FEV1 < 60% of predicted normal values calculatedusing NHANES III reference equations at Screening Visit

• At least one major exacerbation requiring prednisone in the preceding 12 months. Ifpatients are currently well controlled by optimizing their sputum cell counts (eosinophils < 2%), they should have documented history of exacerbations when theireosinophilia was uncontrolled.

• A signed and dated written informed consent prior to study participation.

• Smoking History: Current or former cigarette smokers with a history of cigarettesmoking of greater than 10 pack-years [number of pack years = (number of cigarettesper day/20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]. Former smokers are defined as those who havestopped smoking for at least 6 months prior to Screening Visit

• Male or female adults. A female is eligible to enter and participate in the study ifshe is either of Non-child bearing potential or is of child bearing age and has anegative pregnancy test at screening, and agrees to acceptable contraceptive methodsused consistently and correctly

Exclusion Criteria:

• Current asthma (12% reversibility to a bronchodilator)

• Sputum eosinophils < 3% on fluticasone (or equivalent) of 250µg bid.

• Inability to use salmeterol or tiotropium

• Significant co-morbidity that prevents from participating in the study

• Known bronchiectasis or immune deficiency disorders that would predispose thepatients to recurrent infections.

• Pregnancy or intent to become pregnant and lactating females

• Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit