Sputum-derived Cellular Targets After Xolair (Omalizumab)

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Omalizumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: 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.; Other Names: Saline
Experimental: Omalizumab	Drug: 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.; Other Names: Xolair; corticosteroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome 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 Newly Identified sHBEC Targets (Gene Expression) Analyzed Using Gene Analyses	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

Collaborators and Investigators

• Sponsor: NYU Langone Health

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): July 19, 2018
• Study Completion (Actual): July 19, 2018

Study Registration Dates

• First Submitted: December 17, 2015
• First Submitted That Met QC Criteria: January 19, 2016
• First Posted (Estimate): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: asthma; corticosteroids; Xolair; long-acting beta-agonists
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: 14-01160

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes