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

• Incidence of dosing reactions to milk OIT [ Time Frame: During the Escalation and Maintenance Phases ] [ Designated as safety issue: Yes ]
• Incidence of severe hypersensitivity reactions to milk OIT [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
• Maximum tolerated dose of milk oral immunotherapy and the time required to achieve it [ Time Frame: 22-40 weeks ] [ Designated as safety issue: Yes ]
• Percentage of subjects developing desensitization to milk [ Time Frame: at month 28 ] [ Designated as safety issue: No ]
• Change in endpoint milk skin test titration and mechanistic assays to evaluate biologic responses [ Time Frame: at months 32 ] [ Designated as safety issue: No ]

• Incidence of dosing reactions [ Designated as safety issue: Yes ]
• Incidence of severe hypersensitivity reactions [ Designated as safety issue: Yes ]
• Maximum tolerated dose of milk oral immunotherapy [ Designated as safety issue: Yes ]
• Percentage of subjects developing desensitization to milk [ Designated as safety issue: No ]
• Mechanistic assays to evaluate biologic responses [ Designated as safety issue: No ]

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.

• Biological: Xolair® (omalizumab) placebo/milk OIT
  Placebo for Xolair for 4 months followed by 12 months of milk OIT. after unblinding, will discontinue placebo for Xolair and continue milk OIT for an additional 12 months.
  Other Name: Xolair® (omalizumab) placebo/milk OIT
• Biological: Xolair® (omalizumab)/milk OIT
  Xolair for 4 months followed by 12 months of milk OIT. After unblinding, will continue receiving Xolair along with milk OIT for an additional 12 months.

• Experimental: Xolair® (omalizumab)/milk OIT
  Xolair for 4 months followed by 12 months of milk OIT. After unblinding, will continue receiving Xolair along with milk OIT for an additional 12 months.
  Intervention: Biological: Xolair® (omalizumab)/milk OIT
• Placebo Comparator: Xolair® (omalizumab) placebo/milk OIT
  Placebo for Xolair for 4 months followed by 12 months of milk OIT. after unblinding, will discontinue placebo for Xolair and continue milk OIT for an additional 12 months.
  Intervention: Biological: Xolair® (omalizumab) placebo/milk OIT
• No Intervention: Untreated control
  no intervention.

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 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 IgE level within the previous 12 months (UniCAP > = 0.35 kUA/L)

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:

  • FEV1<80% with or without controller medications
  • 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 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, IM, or IV for indications other than asthma for greater than 3 weeks in the past 6 months