Asthma
Conditions
Keywords
Xolair, corticosteroids, asthma, long-acting beta-agonists
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.
Interventions
DRUGOmalizumab
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.
DRUGPlacebo
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.
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 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 Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma | 16 Weeks of Treatment of omalizumab or placebo |
Secondary
| Measure | Time frame |
|---|---|
| Change in Lung Function Measure by Spirometry Test | 16 Weeks of Treatment of omalizumab or placebo |
| 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 Measures of Small Airway Dysfunction Using Impulse Oscillometry | 16 Weeks of Treatment of omalizumab or placebo |
Other
| Measure | Time frame |
|---|---|
| The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Cufflinks. | 16 Weeks of Treatment of omalizumab or placebo |
| The Effect of Omalizumab on Gene Signature Generation Analyzed Using Gene Analysis Techniques | 16 Weeks of Treatment of omalizumab or placebo |
| The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Gene Analyses | 16 Weeks of Treatment of omalizumab or placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Omalizumab: 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. | 3 |
| Placebo Placebo: 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. | 0 |
| Total | 3 |
Baseline characteristics
| Characteristic | Omalizumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 0 / 3 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 0 / 0 |
Outcome results
Primary
Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Primary
Measurement in the Reduction of the Effect of Omalizumab on IL-33 Gene Expression Using Two Group T-test in Moderate Persistent Asthma
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Primary
Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Nonparametric Wilcoxon in sHBEC in Moderate Persistent Asthma
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Primary
Measurement in the Reduction of the Effect of Omalizumab on Thymic Stromal Lymphopoietin (TSLP) Using Two Group T-test in Moderate Persistent Asthma
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: Most (n=124) of these patients failed screening criteria and investigator did not move forward
Secondary
Change in Lung Function Measure by Spirometry Test
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Change in Measures of Small Airway Dysfunction Using Impulse Oscillometry
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
Change in Score on Asthma Control Test
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Secondary
The Effect of Omalizumab on Changes sHBEC Targets (Gene Expression Array) Compared Using Two-group T-test if Data
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Other Pre-specified
The Effect of Omalizumab on Gene Signature Generation Analyzed Using Gene Analysis Techniques
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Other Pre-specified
The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Cufflinks.
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Other Pre-specified
The Effect of Omalizumab on Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Gene Analyses
Time frame: 16 Weeks of Treatment of omalizumab or placebo
Population: No data displayed because Outcome Measure has zero total participants analyzed.