Clinical trial NCT00461097: Oral Immunotherapy for Childhood Egg Allergy
Official title: Oral Desensitization to Egg With Subsequent Induction of Tolerance for Egg-Allergic Children (CoFAR 3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypersensitivity
Immediate Hypersensitivity
Food Hypersensitivity
Keywords: Egg Allergy
Egg Oral Immunotherapy (OIT)
Food Allergy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Consortium of Food Allergy Research
First posted: 2007-04-17
Enrollment: 55
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg
timeFrame: At the 2 year time point; Egg OIT participants must be approximately 4-6 weeks post-discontinuation of therapy
Secondary outcomes:
measure: Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid
timeFrame: Following the blinded desensitization phase at approximately Week 44
measure: Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation
timeFrame: Initial day of dosing
measure: Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg
timeFrame: Following the blinded desensitization phase at approximately Week 44
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Baseline through the 2-year primary endpoint
measure: Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid
timeFrame: 4 years (48 months)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas Children's Hospital Research Institute
state: Arkansas
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hills
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Wesley Burks, MD
role: STUDY_CHAIR
affiliation: Allergy/Immunology Department, Arkansas Children's Hospital
name: Stacie Jones, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Robert Wood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Scott Sicherer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: David Fleischer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baral VR, Hourihane JO. Food allergy in children. Postgrad Med J. 2005 Nov;81(961):693-701. doi: 10.1136/pgmj.2004.030288.
citation: Sicherer SH, Sampson HA. 9. Food allergy. J Allergy Clin Immunol. 2006 Feb;117(2 Suppl Mini-Primer):S470-5. doi: 10.1016/j.jaci.2005.05.048.
citation: Wood RA. The natural history of food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1631-7.
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 in children. N Engl J Med. 2012 Jul 19;367(3):233-43. doi: 10.1056/NEJMoa1200435.
citation: Jones SM, Burks AW, Keet C, Vickery BP, Scurlock AM, Wood RA, Liu AH, Sicherer SH, Henning AK, Lindblad RW, Dawson P, Berin C, Fleischer DM, Leung DYM, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy. J Allergy Clin Immunol. 2016 Apr;137(4):1117-1127.e10. doi: 10.1016/j.jaci.2015.12.1316. Epub 2016 Mar 9.