Therapeutic Utility of Xolair in Patients Undergoing Aspirin Desensitization

Condition(s) targeted: Aspirin Sensitive Rhinosinusitis/Asthma

Intervention: omalizumab (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: David Lang

Official(s) and/or principal investigator(s):
David M. Lang, M.D., Principal Investigator, Affiliation: The Cleveland Clinic, Department of Allergy and Immunology

Overall contact:
Bette Maierson, BA RRT, Phone: 216/444-2901, Email: maierse@ccf.org

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: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome: Spirometry (FEV1) testing to assess the efficacy of Xolair on aspirin induced bronchospasm during aspirin desensitization in patients with AERD.

Secondary outcome: Changes in serum and urinary markers of eosinophil activation during desensitization and change in urinary LTE4 during bronchospasm. Assessment of aspirin dose that provokes reaction.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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. patients will have exhibited ≥ 12% increase in FEV1 following bronchodilator. 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.

Bette Maierson, BA RRT, Phone: 216/444-2901, Email: maierse@ccf.org

The Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Bette Maierson, BA RRT, Phone: 216-444-2901, Email: maierse@ccf.org
David M Lang, M.D., Principal Investigator

Starting date: May 2006
Last updated: August 2, 2012