Therapeutic Utility of Xolair in Patients Undergoing Aspirin Desensitization

Study Overview
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Brief Summary
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This is a 24 week double-blind study in which subjects will be randomized 2:1 to receive Xolair (Omalizumab) or placebo. 14 subjects will receive Xolair and 7 will receive placebo. Xolair injections will occur every 2-4 weeks. Aspirin desensitization will occur several weeks later. One month after desensitization, the final visit will occur in the GCRC. We hypothesize that administration of Xolair, a monoclonal anti-IgE antibody, prior to the aspirin desensitization will reduce severity of aspirin-induced reaction.

Detailed Description
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This is a 24 week double-blind study consisting of up to 11 office visits for people 18 years of age with aspirin exacerbated respiratory disease (AERD). 21 subjects will participate and will be randomized 2:1 to receive Xolair (Omalizumab) or placebo. 14 subjects will receive Xolair and 7 will receive placebo. Xolair is a FDA approved medication for the treatment of moderate to severe allergic asthma. Injections will occur every 2-4 weeks, for 16 weeks. The dosage will be based upon IgE and body weight. Aspirin desensitization will occur 1-3 weeks later. One month after desensitization, the final visit will occur in the GCRC. Properly selected patients with aspirin exacerbated respiratory disease (AERD) experience benefit in the course of their disease with aspirin desensitization treatment; however, AERD patients are at risk for potentially serious asthmatic reaction when undergoing aspirin desensitization. For this reason, this procedure is currently performed in a monitored setting. We hypothesize that administration of Xolair, a monoclonal anti-IgE antibody, prior to the aspirin desensitization will reduce severity of aspirin-induced respiratory reaction, and that ultimately, use of Xolair will permit this procedure to be performed safely in outpatient settings. This protocol also entails obtaining blood and urine samples to assess the influence of Xolair, compared with placebo. As aspirin induced reaction occurs via heightened release of leukotrienes combined with greater end organ responsiveness to these mediators, we also will be quantifying the impact of prior administration of Xolair, compared with placebo, on the elevation of urinary LTE4 in association with aspirin challenge and with aspirin provoked reaction.

Official Title
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A Placebo Controlled, Double-Blind Investigation of the Therapeutic Utility of Xolair (Omalizumab) for Attenuating Aspirin Induced Bronchospasm in Patients With Aspirin Exacerbated Respiratory Disease (AERD) Undergoing Aspirin Desentization

Conditions
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Aspirin Sensitivity

Intervention / Treatment
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* Drug: Omalizumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years. Fulfill diagnostic criteria for AERD (described below), and be a candidate for aspirin desensitization chronic asthma - frequently moderate-severe or severe patients will have history compatible with variable airflow obstruction. chronic rhinosinusitis - usually requiring previous sinus surgery procedure(s). sinusitis will have been confirmed by imaging studies presently and/or in the past. history of adverse reaction to aspirin and/or aspirin-like drugs (e.g., ibuprofen, naproxen, etc.) compatible with AERD. • Candidate for Xolair [Omalizumab] Moderate-severe persistent asthma IgE = 30-700 IU/ml IgE mediated (allergic) potential to inhalant allergen(s) by cutaneous or in vitro testing. Exclusion Criteria: Women of childbearing potential not using appropriate contraception method(s) Women currently breastfeeding Women who desire to become pregnant during the time of participation in this study Men who desire to get someone pregnant during participation in this study Known sensitivity to Xolair [Omalizumab]. IgE level < 30 IU/ml, or > 700 IU/ml. No evidence of atopy by immediate hypersensitivity skin testing Use of any other investigational agent in the last 30 days Age < 18 years. Current tobacco habituation. Presence of emphysema Ethanolism or drug abuse within last 12 months. Presence of significant medical condition including malignancy, neurologic, kidney, gastrointestinal, liver or cardiovascular disease extensive travel commitments during the study that would interfere with study measurements or clinic visits.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Group<br>Subjects randomized to placebo | Drug: placebo<br>* Subjects randomized to Placebo prior to aspirin desensitization<br>|
| Active Comparator: Omalizumab Group<br>Subjects randomized to omalizumab | Drug: Omalizumab<br>* Subjects randomized to Omalizumab prior to aspirin desensitization<br>* Other names: Xolair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Without Respiratory Reaction During Aspirin Desensitization | Lack of Respiratory reaction during aspirin desensitization, including Spirometry (FEV1) testing, to assess the efficacy of Xolair on attenuating aspirin induced bronchospasm in patients with AERD. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurements of Urinary LTE4 in Association With Respiratory Reaction During Aspirin Desensitization | Measurements of urinary LTE4 in association with aspirin desensitization, comparing subjects randomized to placebo with subjects randomized to omalizumab, with study drug administered for 16 weeks. Measurements were compared for respiratory reaction in placebo subjects who exhibited either upper or lower airway reaction and after 100 mg aspirin challenge dose in omalizumab subjects who were non-reactors. For this analysis, the two omalizumab subjects who had respiratory reaction were not included. | Approximately 24 weeks |