Sputum-derived Cellular Targets After Xolair (Omalizumab)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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In Situ Analysis of Sputum-derived Cellular Targets After Xolair (Omalizumab).

Conditions
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Asthma

Intervention / Treatment
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* Drug: Omalizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab<br> | Drug: Omalizumab<br>* 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.<br>* Other names: corticosteroids;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Two Group T-test in Moderate Persistent Asthma |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma |  | 16 Weeks of Treatment of omalizumab or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of Omalizumab on Changes sHBEC Targets (Gene Expression Array) Compared Using Two-group T-test if Data |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Change in Score on Asthma Control Test |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Change in Lung Function Measure by Spirometry Test |  | 16 Weeks of Treatment of omalizumab or placebo | 
| Change in Measures of Small Airway Dysfunction Using Impulse Oscillometry |  | 16 Weeks of Treatment of omalizumab or placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xolair, corticosteroids, asthma, long-acting beta-agonists