Therapeutic Utility of Xolair in Patients Undergoing Aspirin Desensitization

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.

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.