Sputum-derived Cellular Targets After Xolair (Omalizumab)

This is a randomized, placebo-controlled, double blind, 16-week intervention study to show
feasibility and proof of concept. Analysis of whole induced sputum is under development for
endotyping for asthma, allowing sampling of rare cells from conducting airways, repeated
sampling, and cell-specific detailed genomic evaluation. Investigators have developed a novel
technique to simultaneously enrich innate immune cells from sputum. This technique allows for
in situ analyses of sputum-derived human bronchial epithelial cells (sHBEC). The non-invasive
nature of the technique provides a unique tool for in vivo human studies.

Inclusion Criteria:

- Physician diagnosed asthma

- Lung function (one or more of the following documented in the 5 years before
enrollment or demonstration during screening) 1. Bronchial hyper responsiveness (BhR)
confirmed by ≥ 12% improvement in FEV1 post bronchodilator within the previous 5
years, or 2. Methacholine PC20 < 16mg/dl within the previous 5 years

- Severity Criteria: Moderate-persistent asthma defined by the American Thoracic Society
(ATS)

- Asthma Control: Partly or uncontrolled asthma according to GINA 2012 guidelines (at
least three of the following features: daytime symptoms more than 2 times/week,
limitation of activities, nocturnal symptoms, need for rescue inhaler > 2 times/week,
FEV1 <80% predicted)

- Stable use of moderate-high dose inhaled corticosteroids in previous 3 months
(definition derived from GINA 2012 guidelines: e.g. fluticasone propionate >250
mcg/day, budesonide > 400mcg/day)

- Ability to perform induced sputum maneuvers

- Presence of elevated allergen IgE to any perennial aeroallergen

Exclusion Criteria:

- Pulmonary function: FEV1 ≤ 70% predicted

- Any major chronic illness including but not limited to Chronic Obstructive Pulmonary
Disease (COPD), uncontrolled hypertension, coronary artery disease, bronchiectasis,
congestive heart failure, stroke, cystic fibrosis, insulin-dependent diabetes
mellitus, renal failure, liver disorders, immunodeficiency state, or other condition
that would interfere with participation in the study

- Current or > 10 pack a year pack-year tobacco use

- Any investigational study within previous 1 month

- Inability to perform baseline measurements

- Inability to contact by telephone

- Pregnancy at screening and failure to use double barrier pregnancy protection in woman
of childbearing age

- Hypersensitivity reaction to omalizumab in the past

- Exceeds limits of dosing table (IgE <30 or 700 IU/ml) or body weight of <30 or > 150kg

- Systemic corticosteroids within the previous month

- Known malignant neoplasm