Baked Egg or Egg Oral Immunotherapy for Children With Egg Allergy

Food allergy affects 6-8 percent of children in the United States. In young children, reactions to egg can range from hives to severe life threatening allergic reactions called anaphylaxis. Current treatment for food allergy is complete avoidance of the food and to carry antihistamines and self-injectable epinephrine if an accidental reaction occurs. 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 immunotherapy injections for food allergy are associated with a high rate of allergic reactions, alternate approaches to treatment are needed. Oral (by mouth) immunotherapy (OIT) is one approach that has been tried in some studies in the treatment of food allergies. The purpose of this study is to compare baked foods with egg versus (vs.) egg OIT. The intent of the study is to investigate if participants will be able to consume egg after taking baked foods with egg or egg OIT for a period of time and then stopping for a certain period. This is referred to as tolerance or sustained unresponsiveness. This study will evaluate the effectiveness of the egg OIT vs. baked egg by having each participant ingest egg white solid or baked foods with egg. This will be done over 2 years.

This study will last 2 years. All eligible subjects will receive a baked egg oral food challenge (OFC). Those who pass the baked egg OFC will then have a 2 gm egg OFC. Those who react to the egg OFC will be randomized to Baked Egg or Egg OIT. Individuals who do not pass the initial baked egg OFC will be assigned to Egg OIT. Those who pass the egg OFC will not be eligible for the study and will be followed per site standard of care. All eligible and enrolled subjects will have a 1-year and a 2-year OFC.

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

• Egg Oral Immunotherapy (Drug), also known as Egg white solid: Commercially available egg white solid dispensed by the central manufacturer. Study product will be dispensed in vials for low doses, capsules for mid-range doses, and bulk powder with dosing scoops for the higher doses.
• Baked Egg (Drug): Predetermined food substances with known amounts of Baked Egg (egg protein) with standardized dosing/consumption instructions.

Primary outcomes

• Sustained Unresponsiveness to Egg Consumption at 2 Years. [2 Years]: Sustained unresponsiveness - able to successfully consume 7444 mg egg white protein in a desensitization OFC and, after an 8-10 week egg-free interval, were also able to successfully consume 7444 mg egg white protein in an OFC after up to 2 years of therapy.

Secondary outcomes

• Desensitization to >= 4.444 Grams Egg White Solid. [1 Year and 2 Years]: Development of desensitization to able to successfully consume >=4444 mg egg white protein during a desensitization OFC on therapy at 1 year and 2 years.
• Incidence of All Serious Adverse Events [up to 3 years]: Incidence of all serious adverse events during the study. No statistical analyses were performed since there were no events in 2 of the 3 treatment groups and only 1 event in the third so it would not be meaningful.
• Number of Participants With Unrestricted Consumption of Unbaked Egg [3 years after randomization]: Number of participants who reported consumption of concentrated (unbaked) egg in their diet on the long-term follow-up questionnaire 3 years after randomization, indicating unrestricted consumption of unbaked egg. This is a qualitative questionnaire asking participants about egg in their diet, symptoms, and what treatment they received for their allergic reactions.

Other outcomes

• Changes in Egg-specific Mechanistic Measures and Skin Prick Test Results. [2 Years]: Changes in egg-specific IgE and IgG4, changes in SPT mean wheal diameters, basophil reactivity, Th2 and Treg values.

Sex: All, ages: 3 Years to 16 Years

Inclusion Criteria:

* Age 3 through 16 years with a serum IgE to egg of >= 5 kUA/L within the past 12 months\]
* Reacting to the initial baked egg OFC with dose limiting symptoms OR
* Reacting on a 2 gm egg OFC with dose limiting symptoms to a cumulative dose of 2 gm or less after passing the initial baked egg OFC
* Written informed consent from subject and/or parent/guardian
* Written assent from all subjects as appropriate
* All females of child bearing age must be using appropriate birth control

Exclusion Criteria:

* History of anaphylaxis to egg resulting in hypotension, neurological compromise or mechanical ventilation
* Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes)
* Active eosinophilic gastrointestinal disease in the past 2 years
* Participation in any interventional study for the treatment of food allergy in the past 6 months
* Subject is on "build-up phase" of immunotherapy (i.e., has not reached maintenance dosing). Subjects tolerating maintenance allergen immunotherapy can be enrolled.
* Severe asthma, or uncontrolled mild or moderate asthma. More information on these exclusion criteria can be found in the protocol.
* Inability to discontinue antihistamines for initial day escalation, skin testing or OFC
* Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy (e.g. infliximab, rituximab, etc.) within the past year
* Use of Beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
* Use of investigational drug within 90 days or plan to use investigational drug during the study period
* Pregnancy or lactation

Participant flow

Outcome results

• Sustained Unresponsiveness to Egg Consumption at 2 Years. (Primary), Count of participants, Participants: Baked Egg Randomized 3; Egg OIT Randomized 10; Egg OIT Assigned 7 (p 0.009)
• Desensitization to >= 4.444 Grams Egg White Solid. (Secondary), Count of participants, Participants: Baked Egg Randomized 8; Egg OIT Randomized 17; Egg OIT Assigned 22 (p <0.0001)
• Incidence of All Serious Adverse Events (Secondary), Count of participants, Participants: Baked Egg Randomized 0; Egg OIT Randomized 0; Egg OIT Assigned 1
• Number of Participants With Unrestricted Consumption of Unbaked Egg (Secondary), Count of participants, Participants: Baked Egg Randomized 4; Egg OIT Randomized 14; Egg OIT Assigned 12 (p 0.003)
• Changes in Egg-specific Mechanistic Measures and Skin Prick Test Results. (Other pre specified)

Adverse events

Time frame: up to 3 years, through last clinic visit.

Serious adverse events by term

Other adverse events by term

10 more terms not shown.

• Statistical Analysis Plan (PDF, 2018-04-16)
• Study Protocol (PDF, 2016-02-16)

• Hugh A Sampson, MD, Study chair, Icahn School of Medicine at Mount Sinai
• Robert Wood, MD, Principal investigator, Johns Hopkins University

NIH grants: U19AI066738