Oral Immunotherapy for Childhood Egg Allergy

Hypersensitivity Clinical Trial

Official title:

Oral Desensitization to Egg With Subsequent Induction of Tolerance for Egg-Allergic Children (CoFAR 3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461097
• Other study ID #: DAIT CoFAR3
• Secondary ID: COFARU19AI066738
• Status: Completed
• Phase: Phase 2
• First received: April 16, 2007
• Last updated: November 15, 2017
• Start date: May 2007
• Est. completion date: December 2013

Study information

• Verified date: November 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if oral immunotherapy (OIT) will desensitize a child with an allergy to egg and eventually lead to the development of tolerance to egg.

Description:

In the United States, as many as 6% to 8% of children are affected by food allergy. In young children, allergic reactions to egg can range from mild rash to systemic anaphylaxis. The usual standard of care for allergy is complete avoidance of this food allergen and treatment of accidental systemic reactions by access to self-injected epinephrine. However, accidental exposure to allergens in processed foods may be difficult to avoid. Currently, several therapeutic strategies are being investigated to prevent and treat food allergies. Since standard injection (under the skin) immunotherapy for food allergy is associated with a high rate of allergic reactions, a few studies have recently tried oral immunotherapy (OIT) in food allergy. The purpose of this study is to determine the safety and efficacy of the administration of OIT. The intent is to develop desensitization and eventually tolerance to egg allergen. This study will evaluate tolerance to egg white solid that may be gained by gradually increasing the amounts of egg white solid given to a child over a long period of time.

This study will last up to 48 months. The participants will be randomly assigned to receive oral immunotherapy treatment with egg white solid or placebo. This study will include dose escalation and maintenance followed by oral food challenge (OFC).

For participants receiving egg OIT, visit 1 consists of multiple small incremental doses of egg white solid. This is followed by 32-40 weeks of gradual dose escalation to a stable maintenance dose of egg white solid for at least 8 weeks. At approximately Week 44, participants are given an OFC using 5 grams of egg white solid to identify desensitized individuals. Participants and study staff are unblinded following this initial OFC. Maintenance egg OIT therapy is continued for an additional 1-3 years. Oral Food Challenges with 10 grams of egg white solid will be performed for participants on maintenance egg OIT at subsequent time points (approximately Week 96 and annually thereafter) to test for desensitization. If passed, a repeat OFC after being off therapy for 4-6 weeks will be performed to test for tolerance. An OFC to test for tolerance will use 10 grams of egg white solid and be followed by an open feeding of egg.

Participants receiving placebo during dose escalation and maintenance are given an OFC using 5 grams of egg white solid to test for desensitization at approximately 44 weeks. They are unblinded at that time, continue on an egg-restricted diet, and are followed until up to 2 years. These participants will only receive an OFC at a subsequent time point if their egg Immunoglobulin E (IgE) declines to be less than 2 kilounits of antibody per liter; this OFC will use 10 grams of egg white solid and be followed by an open feeding of egg.

At selected visits, blood and urine collection, physical examination, prick skin tests, and atopic dermatitis and asthma evaluations will occur.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: December 2013
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 18 Years

Eligibility

Inclusion Criteria:

• Convincing clinical history of egg allergy

• Age 6 to 18 years, with a serum IgE [UniCAP] to egg > 5 kUA/L OR

• Age 5 to 6 years, with a serum IgE [UniCAP] to egg = 12kUA/L

• Parent/guardian willing to provide informed consent

• Willing to use acceptable forms of contraception

Exclusion Criteria:

• History of severe anaphylaxis to egg. More information on this criterion can be found in the protocol.

• Known allergy to corn

• Chronic disease requiring therapy (e.g., heart disease, diabetes). Participants who have asthma, atopic dermatitis, or rhinitis are not excluded.

• Participation in any interventional study for the treatment of food allergy in the 6 months prior to study entry

• Participant is on "build-up phase" of immunotherapy and has not reached maintenance dosing. Participants tolerating maintenance allergen immunotherapy are not excluded.

• Severe asthma, uncontrolled mild or moderate asthma. More information on this criterion can be found in the protocol.

• Inability to discontinue antihistamines for the initial day of escalation, skin testing, and OFC

• Omalizumab or other nontraditional forms of oral or sublingual allergen immunotherapy, immunomodulator therapy, or biologic therapy in the 12 months prior to study entry. Participants who have taken corticosteroids are not excluded.

• Investigational drugs 90 days prior to study entry or planned use of an investigational drug during the study period

• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Food Hypersensitivity
• Hypersensitivity
• Hypersensitivity, Immediate
• Immediate Hypersensitivity

Intervention

Drug:
• Egg oral immunotherapy
Egg white solid powder
• Control Group
Placebo for egg white solid

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of North Carolina	Chapel Hills	North Carolina
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	University of Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Consortium of Food Allergy Research

Country where clinical trial is conducted

United States, 

References & Publications (4)

Baral VR, Hourihane JO. Food allergy in children. Postgrad Med J. 2005 Nov;81(961):693-701. Review. — View Citation

Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, Stablein D, Henning AK, Vickery BP, Liu AH, Scurlock AM, Shreffler WG, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Oral immunotherapy for treatment of egg allergy i — View Citation

Sicherer SH, Sampson HA. 9. Food allergy. J Allergy Clin Immunol. 2006 Feb;117(2 Suppl Mini-Primer):S470-5. Review. — View Citation

Wood RA. The natural history of food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1631-7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg	Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were then given an open feeding of egg and those who successfully consumed the open feeding of egg were counted as successes.	At the 2 year time point; Egg OIT participants must be approximately 4-6 weeks post-discontinuation of therapy
Secondary	Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid	Desensitization assessment: Participants who successfully consumed without dose-limiting symptoms 5,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were counted as successes.	Following the blinded desensitization phase at approximately Week 44
Secondary	Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation	On the initial day of dosing, participants were offered 0.1 mg of egg white solid or placebo followed by an approximate doubling every 30 minutes up to a 50 mg dose providing limiting reactions do not occur.	Initial day of dosing
Secondary	Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg	For participants whose maximum tolerated dose on the initial escalation day was less than 50 mg, doses were doubled every 2 weeks up to 50 mg. After 50 mg, dosing was increased to 75 mg, and then dosing increased by 25% until the 2000 mg dose was reached. The maximum time allowed for the build-up phase was 40 weeks; the dose achieved at 40 weeks was considered the maintenance dose.	Following the blinded desensitization phase at approximately Week 44
Secondary	Number of Participants With Serious Adverse Events (SAEs)	This study graded the severity of Adverse Events experienced by participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.	Baseline through the 2-year primary endpoint
Secondary	Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid	Tolerance Assessment: Participants in the Egg OIT treatment arm who were not tolerant at 2 years were offered an additional 2 years of therapy. A 10,000 mg double-blind placebo controlled oral food challenge to egg was done the same way as the one performed at 2 years for these participants in order to identify tolerant individuals in the 2 to 4 year extension segment. The tolerant individuals from this segment were then added to the tolerant individuals from the 2 year segment.	4 years (48 months)