Predicting the Clinical Response to Omalizumab With Anti-Immunoglobulin E (IgE) Ab Response or Syk Expression in Basophils

From a therapeutic perspective, the study will determine whether changes in the peripheral
blood basophil response to crosslinking anti-IgE Ab during treatment with omalizumab predicts
the clinical efficacy of treatment with the drug. Secondary outcomes measures would focus on
whether the starting level of anti-IgE-mediated histamine release, or the changes syk
expression or its starting level would be sufficient to predict the clinical outcome.

The study is a single-site trial to evaluate the utility of baseline basophil measures to
predict the efficacy of subcutaneously administered omalizumab as an add-on therapy for the
treatment of adult patients 18−75 years old who have been diagnosed with moderate to severe
asthma according to current approved guidelines. Patients will be treated with omalizumab
according to the standard FDA approved dosing table for a period of 16 weeks.

Inclusion Criteria:

- Patients with moderate-to-severe asthma; male and females aged 18-75 who are
symptomatic despite treatment with inhaled corticosteroids if they also had an asthma
duration > 1 year.

- Positive blood testing to at least one common allergen (including must mite, D. F. and
D. P., cockroach, dog or cat)

- Serum IgE within the bounds of the dosing table (>30 IU/ml to < 700 IU/ml)

- Reversibility of > 12% within 30 minutes after administration of albuterol or history
of reversibility in past or history of positive methacholine in past

- Baseline Forced expiratory volume (FEV1) of > 0% and < 80% of predicted

- Treatment with 400 to 800 ug day of beclomethasone dipropionate or its equivalent.

- Patients must be willing to give written informed consent and be able to adhere to
dose and visit schedules and meet trial requirements.

- Patients will be excluded if they have prior sensitivity to omalizumab, and acute
respiratory tract infection prior to or during the run-in period, or a need for
regular B-agonist use.

Exclusion Criteria:

- Treatment with an investigational agent within 30 days of screening

- Previously treated with omalizumab within a year prior to screening

- Treatment 1 month prior to screening with: hydroxychloroquine, methotrexate,
cyclosporine, cyclophosphamide, intravenous immunoglobulin G, and plasmapheresis

- Clinically relevant laboratory anomalies at screening including individuals with
reduced hematocrit (<32%), White Blood Cell (WBC) count (2400/microliter), platelet
count (< 75000/microliter), and increased creatinine (> 141.4 micromolar/L), or
aminotransferase (AST) (>100 IU/L).

- Patients with current malignancy, history of malignancy, or currently under work-up
for suspected malignancy, or bleeding disorder.

- History of any medical condition that is unstable

- Inability to comply with study and follow-up procedures

- Patients may not take systemic corticosteroids within 2 weeks prior to screening\

- Women of childbearing potential who are pregnant or nursing mothers, or who are of
childbearing potential (post-menarche) and are not practicing an acceptable form of
contraception ( as determined by the site investigator)

- Individuals with body weight less than 30 kg or greater than 150 kg.