OIT and Xolair® (Omalizumab) in Cow's Milk Allergy

Status:	Completed
Conditions:	Allergy, Neurology
Therapuetic Areas:	Neurology, Otolaryngology
Healthy:	No
Age Range:	7 - 35
Updated:	4/21/2016
Start Date:	August 2010
End Date:	October 2015

Oral Immunotherapy Combined With Humanized Monoclonal Anti-IgE Antibody Xolair® (Omalizumab)in the Treatment of Cow's Milk Allergy

Food allergy affects up to 4% of the U.S. population and is most common in young children.
Milk allergy is the most common cause of food allergy in infants and young children, and
usually develops in the first year of life. There is no treatment for food allergy and the
current standard of care for milk-allergic individuals is the avoidance of milk-containing
products. Research is underway to identify potential therapeutic strategies to reduce or
eliminate the adverse effects experienced by milk-allergic individuals when they consume
milk-containing products.

Several studies have suggested that milk-allergic children who receive milk protein oral
immunotherapy (OIT) may become desensitized to milk, resulting in short term protection
against accidental ingestion of milk products. However, these children did not develop
"tolerance," which is long term protection even after milk immunotherapy is stopped. A
potential strategy to induce tolerance to milk uses milk in combination with Xolair®
(omalizumab). Xolair consists of anti-IgE molecules that attach to IgE, the major antibody
involved in allergic reactions. The goal of this clinical trial is to see whether Xolair® in
combination with milk protein OIT is safer and more effective than OIT alone in inducing
tolerance to milk and milk products. Participants will be administered a double blind,
placebo controlled milk challenge at various time points in the study. If desensitization is
achieved participants will be tested for tolerance at a certain time point after stopping
treatment.

Inclusion Criteria:

- Subject and/or parent/ legal guardian must be able to understand and provide written
informed consent

- Written or verbal assent from all study subjects less than 18 years (per site
Institutional Review Board (IRB) regulations)

- 7 to 35 years of age; any gender; any racial and ethnic origin

- No known contraindications to therapy using oral immunotherapy with milk protein or
Xolair® (omalizumab)

- All female subjects of childbearing potential must have a negative pregnancy test
upon study entry

- All treated females of childbearing potential must agree to use FDA approved methods
of birth control for the duration of the study

Active Treatment Subjects:

- Cow's milk allergy confirmed by a positive double-blind placebo controlled milk
challenge (DBPCMC) to a dose of less than 2 g of milk protein within the past 6
months

- A skin prick test positive to milk (diameter of wheal >= 3.0 mm) OR detectable serum
milk specific Immunoglobulin E (IgE) level within the previous 12 months (UniCAP > =
0.35 kUA/L (allergen-equivalent kilounits per liter))

Control Subjects:

• A skin prick test positive to milk (diameter of wheal >= 10.0 mm) OR detectable serum
milk specific IgE level within the previous 12 months (UniCAP >= 15 kUA/L)

Exclusion Criteria:

- A history of life-threatening anaphylaxis to milk (involving hypotension or requiring
mechanical ventilation)

- Known allergy to any components of the placebo for Xolair®

- Chronic disease other than asthma, atopic dermatitis, or allergic rhinitis requiring
therapy (e.g., heart disease, diabetes)

- Use of β-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors,
angiotensin-receptor blockers (ARB), or calcium channel blockers

- Severe asthma

- Mild or moderate asthma with any of the following criteria met:

- Forced expiratory volume in the first second (FEV1) < 80% with or without
controller medications

- Inhaled corticosteroids (ICS) dosing of >500 mcg daily fluticasone (or
equivalent inhaled corticosteroids based on NHLBI dosing chart)

- history of daily oral steroid dosing for >1 month during the past year

- burst oral steroid course in the past 6 months

- more than one burst oral steroid course in the past year

- more than one hospitalization in the past year for asthma, or

- more than one ER visit in the past 6 months for asthma

- Baseline spirometry (or peak flow rate (PFR) if unable to perform spirometry) result
of FEV1<80%

- Pregnancy or lactation. All females of child-bearing age will undergo pregnancy
testing. All treated females will confirm compliance to appropriate birth control
measures throughout the course of the study;

- Participation in any interventional study for the treatment of food allergy in the
past 6 months

- Subject is on a buildup phase of standard subcutaneous immunotherapy for inhalant
allergens (may be enrolled on maintenance dose);

- Use of Xolair® (omalizumab) or other non-traditional forms of allergen immunotherapy
(e.g., oral or sublingual immunotherapy) or immunomodulator therapy (not including
corticosteroids) or biologic therapy within the past year

- Inability to discontinue antihistamines for 5 half-lives prior to routine study tests
(DBPCMC or endpoint titration tests)

- Known sensitivity to Xolair® (omalizumab) or to the class of study drugs

- Baseline serum total IgE over 1,300 IU/mL or body weight more than 150 kg, or
subjects with weight-IgE combination that yields a dose requirement greater than 750
mg (due to limitations of Xolair® (omalizumab) dosing)

- Mental illness or history of drug or alcohol abuse that, in the opinion of the
investigator, would interfere with the subject's ability to comply with study
requirements

- Inability or unwillingness of a subject to give written informed consent or comply
with study protocol

- Use of investigational drugs within 90 days of participation

- Other contraindications to milk oral immunotherapy or Xolair® (omalizumab)

- Recipient of any licensed or investigational live attenuated vaccine(s) within 2
months of enrollment

- Families who do not speak English

- Systemic steroids oral, intramuscular (IM), or IV for indications other than asthma
for greater than 3 weeks in the past 6 months

We found this trial at

sites

Johns Hopkins University School of Medicine

733 North Broadway
Baltimore, Maryland 21205

(410) 955-3182