Oral Immunotherapy for Wheat Allergy

Food allergy affects 6-8 percent of children in the United States. Wheat is one of the eight most common foods inducing allergic reactions in the US. 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 intent of the study is to examine the clinical effects and safety of wheat OIT. This study will last 2 years. All eligible subjects will receive a wheat oral food challenge (OFC). Those who react to 1923mg or less of vital wheat gluten will be randomized to Wheat OIT or a placebo. All eligible and enrolled subjects will have a 1-year and 2-year OFC. Placebo subjects will crossover to Wheat OIT at the 1-year time point. At selected visits, blood and urine collection, physical examination, prick skin tests, and atopic dermatitis and asthma evaluations will occur.

• Wheat OIT (Drug), also known as Vital Wheat Gluten: Vital Wheat Gluten 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.

Primary outcomes

• The Percentage of Desensitized Participants as Measured by the Ability to Consume at Least 4443 mg of Wheat Protein During a 7443 mg Wheat Protein Oral Food Challenge (OFC) Performed 1 Year After Initiating Treatment. [1 Year]: Determine in wheat allergic children, whether relative to placebo, daily oral administration of Vital Wheat Gluten escalated to a maximum of 2035 mg/day of Vital Wheat Gluten increases desensitization as measured by consuming without dose limiting symptoms 4443 mg of wheat protein on a 7443 mg wheat protein OFC performed 1 year after initiating treatment.

Secondary outcomes

• Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge [8 to 10 weeks after passing the 2 Year OFC]: The number of subjects who successfully consume a 7443 mg wheat protein oral food challenge (OFC) 8-10 weeks after therapy discontinuation and after passing the 7443 mg wheat protein OFC at the 2 year time point.This OFC will only be administered to subjects in the initial active treatment group.
• Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT [44 Weeks]: The number of subjects who achieve the targeted maintenance dose of wheat OIT during the desensitization phase of the study. For Wheat OIT group, reached target dose of 2035 mg wheat powder/1445 mg wheat protein. For placebo group, reached target dose of 2035 mg placebo powder.
• Number of Subjects That Achieve Desensitization in the Placebo Cross Over Group [2 Years]: The number of subjects that achieve desensitization in the placebo cross over group after 1 year of dosing. Able to consume at least 4443 mg wheat protein on the Week 52 Crossover OFC (4443 mg wheat protein is the amount that was used for the primary endpoint).
• Incidence of All Serious Adverse Events During the Study. [1 year and 2 Years]

Sex: All, ages: 4 Years to 30 Years

Inclusion Criteria:

* Age 4-30 years either sex, any race, any ethnicity
* Positive Prick Skin Test to wheat greater than 3mm compared to control and/or a wheat specific IgE >= 0.35 kUA/L
* Positive baseline challenge to wheat (<= 1923 mg of vital wheat gluten)
* 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 wheat resulting in hypotension, neurological compromise or mechanical ventilation
* Known allergy to corn
* Known celiac disease
* Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes)
* Active eosinophilic gastrointestinal disease in the past two 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, uncontrolled mild or moderate asthma. More information on this criterion can be found in the protocol.
* A burst of oral, IM or IV steroids of more than 2 days for an indication other than asthma in the past 1 month
* Inability to discontinue antihistamines for initial day escalation, skin testing or OFC
* Use of omalizumab or other non-traditional forms of allergen immunotherapy or immunomodulator therapy (not including corticosteroids) or biologic therapy 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

• The Percentage of Desensitized Participants as Measured by the Ability to Consume at Least 4443 mg of Wheat Protein During a 7443 mg Wheat Protein Oral Food Challenge (OFC) Performed 1 Year After Initiating Treatment. (Primary), Count of participants, Participants: Placebo 0; Wheat OIT 12
• Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge (Secondary), Count of participants, Participants: Placebo Then High Dose Group 0; Wheat OIT 3
• Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT (Secondary), Count of participants, Participants: Placebo Then High Dose Group 21; Wheat OIT 19
• Number of Subjects That Achieve Desensitization in the Placebo Cross Over Group (Secondary), Count of participants, Participants: Placebo Then High Dose Group 14
• Incidence of All Serious Adverse Events During the Study. (Secondary), Count of participants, Participants: Wheat OIT Before 1 Year 0; Placebo Before 1 Year 3; Wheat OIT After 1 Year 1; Placebo Crossover 1

Adverse events

Time frame: 2 years

Serious adverse events by term

Other adverse events by term

3 more terms not shown.

• Hugh A Sampson, MD, Study chair, Icahn School of Medicine at Mount Sinai
• Hugh A Sampson, MD, Principal investigator, Icahn School of Medicine at Mount Sinai