Sputum-derived Cellular Targets After Xolair (Omalizumab)
Condition: Asthma
MeSH terms: Asthma
Intervention: Omalizumab; Placebo
Intervention description: Omalizumab will be dosed according to dosing and U.S. administration guidelines for omalizumab. Omalizumab will be dosed every 2-4 weeks based on the patient's pre treatment serum IgE level (IU/mL) and initial visit body weight (kg). Omalizumab will be delivered as a subcutaneous injection. Standard safety precautions for dosing will be observed, including clinical observation after dosing, and provision of an epinephrine pen. Maintenance asthma treatment will remain unchanged.; Saline with a volume of injection frequency indicated based on the patient's serum IgE and body weight, delivered subcutaneously and supplied by Novartis Pharma.
Intervention MeSH terms: Omalizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Xolair; corticosteroids; asthma; long-acting beta-agonists

Summary:

      The primary purpose of this study is to identify additional mechanisms of action of
      omalizumab that will lead to improved stratification of patients for treatment. Understanding
      the response of specific innate immune effector cells in the lung can provide clues to these
      questions. Investigators will use non-invasive measures of a discrete cell population to
      examine the downstream effects of omalizumab treatment in the lung. Information derived from
      these studies will help clarify mechanisms of action of omalizumab and help identify
      potential tools for patient endotyping and stratification for therapeutic interventions.
    

Eligibility criteria:

        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