Xolair Treatment for Milk Allergic Children

Our hypothesis is that pretreatment with anti-IgE mAb will greatly reduce the side effects
and allergic reactions that occur during oral desensitization to foods and will enhance the
development of oral tolerance in patients with severe milk allergy. Once desensitized to
milk, children will be able to tolerate milk in a Double Blind Placebo Controlled Food
Challenge.

The study will also evaluate whether Xolair provides a robust durability of tolerance once
administration of Xolair is terminated. We will examine the specific immunological mechanisms
that mediate oral tolerance in children undergoing oral milk desensitization

The trial will be conducted in three parts: (1) pre-treatment with Xolair for 8 weeks, (2)
oral desensitization to cow's milk from weeks 9-16 and continued treatment with Xolair for 8
weeks, and (3) double blind placebo controlled food challenge to milk.

Inclusion Criteria:

- Moderate to severe pediatric cow's milk allergy-sensitive subjects between the ages of
4-18 years old.

- Total IgE >30 kU/L

- Sensitivity to cow's milk allergen will be documented by a positive skin prick test
result (see Appendix E for details) and RAST test to cow's milk, with 25 kU/L as a
lower limit of eligibility. Patients who do not meet the cow's milk RAST requirement
may be eligible for this study if they have a history of a moderate to severe
reaction, and if they have recently failed an oral food challenge with milk ordered by
their physician.

- All female subjects of child-bearing potential will be required to provide a urine
sample for pregnancy testing that must be negative one week before being allowed to
participate in the study.

- Subjects must be planning to remain in the study area during the trial.

- Subjects and/or their parents must be trained on the proper use of the Epi-Pen to be
allowed to enroll in the study.

Exclusion Criteria:

- No absolute contraindications to allergen skin testing and/or oral ingestion of milk
are known. However, the risk of serious systemic anaphylactic reactions to milk
suggests a number of preexisting conditions that should be considered relative
contraindications. Among those conditions are acute infections, autoimmune disease,
severe cardiac disease, and treatment with beta-adrenergic antagonistic drugs
(beta-blockers).

- Subjects having a history of severe anaphylaxis to milk requiring intubation or
admission to an ICU, frequent allergic or non-allergic urticaria, or history
consistent with poorly controlled persistent asthma.

- Total IgE > 2000 IU/mL.

- Subjects with unstable angina, significant arrhythmia, uncontrolled hypertension,
chronic sinusitis, or other chronic or immunological diseases that in the mind of the
investigator might interfere with the evaluation or administration of the test drug or
pose additional risk to the subject e.g. gastrointestinal or gastroesophageal disease,
chronic infections, scleroderma, hepatic and gallbladder disease, chronic non-allergic
pulmonary disease.

- Subject with an FEV1 or PEF less than 80% predicted (moderate persistent asthma) with
or without controller medication (if able to perform the maneuver) at screening, the
oral desensitization visit, or food challenge visit.

- Subjects who have received an experimental drug in the last 30 days prior to admission
into this study or who plan to use an experimental drug during the study.

- Subjects who are current users of oral, intramuscular, or intravenous corticosteroids,
tricyclic antidepressants, or are taking a beta-blocker (oral or topical).

- Subjects routinely using medication that could induce adverse gastrointestinal
reactions during the study.

- Subjects refusing to sign the EpiPen Training Form (see Appendix F).

- Pregnant or breast feeding females.

- Subjects with a history of rice and soy allergy.