Eosinophilic Airway Inflammation and Mepolizumab

Inclusion Criteria:

- Males or females age 18 to 50 yrs,

- History of asthma based upon presence of asthma symptoms such as cough, shortness of
breath, wheeze or chest tightness,

- positive skin-prick test to a House Dust Mite extract,

- Forced expiratory volume at one second >70% predicted pre-albuterol, > 80% predicted
post albuterol

- >12% increase in Forced expiratory volume at one second following inhaled albuterol
(180 µg) and/or

- airway responsiveness to methacholine (PC20 <8mg/ml).

- > 20% immediate drop in FEV1 following inhaled antigen challenge.

- Safety laboratory assessments within normal ranges (labs to include complete blood
count with differential, blood urea nitrogen, creatinine, aspartate aminotransferase,
alanine aminotransferase, Prothrombin time, Partial Thromboplastin Time, and platelet
count)

- Female subjects of child-bearing potential must have a negative urine pregnancy test
(urine HCG) within 48 hours of the methacholine challenge at Visit 2 and agree to use
a reliable method of birth control for the duration of the study (reliable methods of
birth control can include abstinence, barrier methods, oral contraceptives, injection
contraceptives or skin absorption contraceptives).

- In the opinion of the investigator, capable and willing to grant written informed
consent and cooperate with study procedures and requirements.

Exclusion Criteria:

- Use of inhaled or systemic corticosteroids or leukotriene inhibitors within 1 month of
screening.

- Treatment with Omalizumab (anti-IgE) within 9 months of screening visit

- Concomitant use of any other monoclonal antibody

- Respiratory infection within 4 weeks of study

- Unstable asthma as indicated by self-report of increased symptoms or increased
beta-agonist use over the previous 2 weeks.

- Female subjects who are pregnant, nursing or have a pregnancy planned during the
course of study

- Current smokers (defined as smoked within the last year) or a former smoker with a
history of >5 pack years.

- Major health problems such as heart disease, type I and II diabetes or lung diseases
other than asthma. Decisions regarding this criteria will be based upon the judgment
of the investigator.

- Previous malignancy.

- Medication other than for asthma, allergies or contraception and that the investigator
feels may interfere with the conduct of study (e.g. monoamine oxidase inhibitors and
B-adrenergic antagonists in any form)

- Known history of allergic reaction to previous antibody administration.

- Prior treatment with an anti-interleukin-5 monoclonal antibody,

- Use of an investigational drug within 30 days of entering the study,

- History of noncompliance with medical regimens or subjects who are considered
unreliable.