Sputum-derived Cellular Targets After Xolair (Omalizumab)

NCT02658877 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 14-01160
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Xolair; corticosteroids; asthma; long-acting beta-agonists

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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 Outcomes (3)

• 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

Study Arms (2)

Omalizumab

EXPERIMENTAL

Drug: Omalizumab

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Omalizumab 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.

Also known as: Xolair, corticosteroids

Omalizumab

Placebo 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.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Omalizumab; Adrenal Cortex Hormones; Sodium Chloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Joan Reibman
• Organization: NYU Langone Health

Joan.Reibman@nyulangone.org

212 263 6479

Study Officials

• Joan Reibman, MD

  New York University Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: January 20, 2016
• Study Start: January 1, 2016
• Primary Completion: July 19, 2018
• Study Completion: July 19, 2018
• Last Updated: September 30, 2019
• Results First Posted: September 30, 2019

Record last verified: 2019-09

Locations

US (1)