OIT and Xolair® (Omalizumab) in Cow's Milk Allergy
Condition: Milk Allergy
MeSH terms: Hypersensitivity; Milk Hypersensitivity
Intervention: Placebo for omalizumab; Omalizumab; Milk powder
Intervention description: Placebo for omalizumab is injected subcutaneously every 2-4 weeks for 16 months at a volume designed to match that of the verum treatment group (determined by the participant's IgE level and weight).; Omalizumab is injected subcutaneously every 2-4 weeks for 28 months at a dose determined by the participants IgE level and weight.; Milk powder is ingested orally at a dosage of up to 3.84 grams of of milk protein daily from Month 4 through Month 28 if the Month 28 10 g milk OFC is failed, and through Month 30 if the Month 28 10 g milk OFC is passed.
Intervention MeSH terms: Omalizumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 77.0
Sex: All
Minimum age: 7 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: food allergy

Summary:

      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.
    

Eligibility criteria:

        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