Xolair Treatment for Milk Allergic Children

Xolair (Omalizumab) Enhances Oral Tolerance Induction in Milk Allergic Children

This is a pilot feasibility study, using Xolair pretreatment for oral milk desensitization. The major assessment will be safety, and the investigators will evaluate for any type of reaction, including allergic reactions that occur during the course of the study.

Study Overview

• Status: Completed
• Conditions: Milk Allergy
• Intervention / Treatment: Drug: omalizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Uneiversity Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hosptial Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xolair; All patients will receive Xolair treatment for 16 weeks.	Drug: omalizumab; Dosing table established for omalizumab; Other Names: Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The major goal of this study is to assess the safety of Xolair in young children, and the safety of oral desensitization in patients pretreated with Xolair	week 53

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Stanford University
• Investigators: Principal Investigator: Dale Umetsu, MD, Boston Children's Hospital

Publications and helpful links

General Publications

• Bedoret D, Singh AK, Shaw V, Hoyte EG, Hamilton R, DeKruyff RH, Schneider LC, Nadeau KC, Umetsu DT. Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab. Mucosal Immunol. 2012 May;5(3):267-76. doi: 10.1038/mi.2012.5. Epub 2012 Feb 8.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: August 27, 2009
• First Submitted That Met QC Criteria: August 27, 2009
• First Posted (Estimate): August 28, 2009

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 29, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Milk Allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: Milk-01