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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.


Detailed Summary:
Sponsor: Hugh A Sampson, MD

Current Primary Outcome: Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk [ Time Frame: Month 32 which is 8 weeks following the discontinuation of milk OIT for both groups and 4 months after discontinuation of omalizumab for the omalizumab group ]

Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of milk protein during a double-blind placebo-controlled oral food challenge were then given an open feeding of milk and those who successfully consumed the open feeding were counted as successes.


Original Primary Outcome: Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk

Current Secondary Outcome:

  • Incidence of Dosing Reactions to Milk OIT During the Escalation Phase [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]
    Any reaction to daily milk OIT dosing recorded by the participant during the Escalation Phase.
  • Incidence of Dosing Reactions to Milk OIT During the Maintenance Phase [ Time Frame: After completion of Escalation Phase at 22 to 40 weeks, the Maintenance Phase lasted up to Month 30 ]
    Any reaction to daily milk OIT dosing recorded by the participant during the Maintenance Phase.
  • Incidence of Severe Hypersensitivity Reactions to Milk OIT [ Time Frame: Through completion of milk OIT dosing (at Month 28 if failed desensitization OFC, at Month 30 if passed desensitization OFC) ]
    Participants who had a change in mental status or hypotension as a milk OIT dosing symptom were counted as having a severe hypersensitivity reaction.
  • Maximum Tolerated Dose of Milk Oral Immunotherapy (OIT) [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]
    Maximum tolerated dose of milk OIT is the highest dose of milk powder the participant was able to consume for at least 14 consecutive days.
  • Percentage of Participants in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Desensitization to Milk [ Time Frame: Month 28 ]
    Desensitization Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of milk protein during a double-blind placebo-controlled oral food challenge were counted as successes.
  • Time to Maximum Tolerated Dose [ Time Frame: Baseline to completion of Escalation Phase at 22 to 40 weeks ]
    Time to reach the maximum tolerated dose (MTD) of milk oral immunotherapy (OIT); MTD is the highest dose of milk powder the participant was able to consume for at least 14 consecutive days.
  • Change From Baseline to Month 32 in Area Under the Curve for Milk Endpoint Titration Prick Skin Test [ Time Frame: Month 32 ]
    A milk endpoint titration is a prick skin test using 5 serial 10-fold dilutions of milk which include 1:20 wt/vol, 1:200 wt/vol, 1:2,000 wt/vol, 1:20,000 wt/vol and 1:200,000 wt/vol. The score for each of these dilutions is calculated by subtracting the diameter of the saline control wheal from the diameter of the milk wheal (in millimeters). The area under the curve is calculated by adding together the scores from all 5 milk dilutions creating a composite score.
  • Change From Baseline to Month 32 in Antigen-specific Immunoglobulin E (IgE) [ Time Frame: Month 32 ]
    The level of milk IgE in plasma as well as the IgE levels of 2 milk proteins, casein and beta-lactoglobulin, were measured. The value for each participant was subtracted from the value for that participant at baseline. Month 32 was the last visit on treatment.
  • Change From Baseline to Month 32 in Antigen-specific Immunoglobulin G4 (IgG4) [ Time Frame: Month 32 ]
    Casein and beta-lactoglobulin milk proteins IgG4 levels were measured in plasma. The value for each participant was subtracted from the value for that participant at baseline. Month 32 was the last visit on treatment.
  • Change From Baseline to Month 38 in Antigen-specific Immunoglobulin E (IgE) [ Time Frame: Month 38 ]
    The level of milk IgE in plasma as well as the IgE levels of 2 milk proteins, casein and beta-lactoglobulin, were measured. The value for each participant was subtracted from the value for that participant at baseline. Month 38 was 6 months after treatment ended at Month 32.
  • Change From Baseline to Month 38 in Antigen-specific Immunoglobulin G4 (IgG4) [ Time Frame: Month 38 ]
    Casein and beta-lactoglobulin milk proteins IgG4 levels were measured in plasma. The value for each participant was subtracted from the value for that participant at baseline. Month 38 was 6 months after treatment ended at Month 32.
  • Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk [ Time Frame: Month 32 ]
    Basophil cells isolated from blood using flow cytometry were stimulated with 5 different levels of milk and the percent of basophil cells that were CD63 positive was measured. The value for each participant obtained at Month 32 was subtracted from the value for that participant at baseline. The 5 different levels of milk stimulant were: 10 µg/mL, 1 µg/mL , 0.1 µg/mL , 0.01 µg/mL , and 0.001 µg/mL. Month 32 was the last visit on treatment.
  • Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk [ Time Frame: Month 38 ]
    Basophil cells isolated from blood using flow cytometry were s

    Original Secondary Outcome:

    • Incidence of dosing reactions
    • Incidence of severe hypersensitivity reactions
    • Maximum tolerated dose of milk oral immunotherapy
    • Percentage of subjects developing desensitization to milk
    • Mechanistic assays to evaluate biologic responses


    Information By: Icahn School of Medicine at Mount Sinai

    Dates:
    Date Received: July 2, 2010
    Date Started: August 2010
    Date Completion:
    Last Updated: December 15, 2016
    Last Verified: December 2016