Sputum-derived Cellular Targets After Xolair (Omalizumab)

NCT ID: NCT02658877

Last Updated: 2019-09-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-07-19

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Omalizumab

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Xolair; corticosteroids; Saline

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joan Reibman, MD

Role: PRINCIPAL_INVESTIGATOR

New York University Medical School

Locations

New York University School of Medicine

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-01160

Identifier Type: -

Identifier Source: org_study_id