Clinical trial NCT02658877: Sputum-derived Cellular Targets After Xolair (Omalizumab)
Official title: In Situ Analysis of Sputum-derived Cellular Targets After Xolair (Omalizumab).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Asthma
Keywords: Xolair
corticosteroids
asthma
long-acting beta-agonists
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2016-01-20
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Two Group T-test in Moderate Persistent Asthma
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
Secondary outcomes:
measure: The Effect of Omalizumab on Changes sHBEC Targets (Gene Expression Array) Compared Using Two-group T-test if Data
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Change in Score on Asthma Control Test
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Change in Lung Function Measure by Spirometry Test
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: Change in Measures of Small Airway Dysfunction Using Impulse Oscillometry
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
Other outcomes:
measure: The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Cufflinks.
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Gene Analyses
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
measure: The Effect of Omalizumab on Gene "Signature" Generation Analyzed Using Gene Analysis Techniques
timeFrame: 16 Weeks of Treatment of omalizumab or placebo
Locations:
city: New York
country: United States
facility: New York University School of Medicine
state: New York
Study officials:
affiliation: New York University Medical School
name: Joan Reibman, MD
role: PRINCIPAL_INVESTIGATOR
References: