Wheat Allergy
Conditions
Keywords
Food Allergy, Wheat Allergy, Oral Immunotherapy
Brief summary
This study is being done to learn about the medical effects, the safety, and the immunologic effects of Wheat Oral Immunotherapy (OIT) treatment. The goal of the study is to find out whether subjects can develop the ability to eat wheat (the food allergen) regularly without allergic symptoms after stopping the study treatment.
Detailed description
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.
Interventions
DRUGWheat OIT
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.
Sponsors
Hugh A Sampson, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Participant flow
Recruitment details
Enrollment began November 2013 and was completed in November 2014
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then High Dose Group 52 weeks placebo, then crossed over to active wheat oral immunotherapy (OIT) to a maximum dose of 3870mg wheat powder (2748 mg wheat protein). Placebo subjects who were crossed over received a higher maintenance dose than the Wheat OIT subjects. After this group received 52 weeks of active wheat OIT treatment, they then completed a Week 52 7443mg wheat protein oral food challenge (OFC). | 23 |
| Wheat OIT 2 years on active wheat oral immunotherapy (OIT) with maximum maintenance dose 2035mg wheat powder (1445mg wheat protein), then completed Year 2 7443 mg wheat protein desensitization oral food challenge (OFC); those that passed this OFC stopped active OIT treatment for 8-10 weeks and then completed the Year 2 7443 mg wheat protein tolerance OFC. | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 52 Weeks Blinded Study Treatment | Dosing Symptoms | 0 | 3 |
| 52 Weeks Blinded Study Treatment | Non-compliance | 1 | 0 |
| 52 Weeks Blinded Study Treatment | Withdrawal by Subject | 1 | 1 |
| 52 Weeks Open Label Active Wheat OIT | Dosing Symptoms | 2 | 0 |
| 52 Weeks Open Label Active Wheat OIT | Lost to Follow-up | 0 | 1 |
| 52 Weeks Open Label Active Wheat OIT | Non-compliance | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Wheat OIT | Placebo Then High Dose Group |
|---|---|---|---|
| Age, Continuous | 8.7 years | 8.6 years | 8.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 23 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Maximum Initial Escalation Day Dose | 12.0 mg powder | 12.0 mg powder | 12.0 mg powder |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Male | 36 Participants | 18 Participants | 18 Participants |
| Wheat IgE | 88.4 kUA/L | 94.1 kUA/L | 86.8 kUA/L |
| Wheat IgG4 | 4.2 mgA/L | 2.9 mgA/L | 4.6 mgA/L |
| Wheat OFC Dose at First Symptom | 13.0 mg protein | 43.0 mg protein | 13.0 mg protein |
| Wheat OFC Successfully Consumed Dose | 43.0 mg protein | 43.0 mg protein | 43.0 mg protein |
| Wheat Skin Prick Test | 6.1 mm STANDARD_DEVIATION 3.2 | 5.3 mm STANDARD_DEVIATION 3.4 | 6.8 mm STANDARD_DEVIATION 2.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 23 / 23 | 21 / 23 | 18 / 22 | 21 / 21 |
| serious Total, serious adverse events | 0 / 23 | 3 / 23 | 1 / 22 | 1 / 21 |
Outcome results
Primary
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.
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.
Time frame: 1 Year
Population: All randomized participants were included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | 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. | 0 Participants |
| Wheat OIT | 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. | 12 Participants |
Secondary
Incidence of All Serious Adverse Events During the Study.
Time frame: 1 year and 2 Years
Population: Data was available for 22 participants in the Wheat OIT group and 21 participants for the Placebo Crossover group at the end of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Incidence of All Serious Adverse Events During the Study. | 0 Participants |
| Wheat OIT | Incidence of All Serious Adverse Events During the Study. | 3 Participants |
| Wheat OIT After 1 Year | Incidence of All Serious Adverse Events During the Study. | 1 Participants |
| Placebo Crossover | Incidence of All Serious Adverse Events During the Study. | 1 Participants |
Secondary
Number of Subjects That Achieve Desensitization in the Placebo Cross Over Group
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).
Time frame: 2 Years
Population: Two Placebo subjects did not crossover. This outcome measure is only for the Placebo crossover group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Subjects That Achieve Desensitization in the Placebo Cross Over Group | 14 Participants |
Secondary
Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT
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.
Time frame: 44 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT | 21 Participants |
| Wheat OIT | Number of Subjects Who Achieve the Targeted Maintenance Dose of Wheat OIT | 19 Participants |
Secondary
Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge
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.
Time frame: 8 to 10 weeks after passing the 2 Year OFC
Population: This is not applicable for the Placebo Crossover subjects as they did not complete at 2 Year Tolerance OFC per the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge | 0 Participants |
| Wheat OIT | Number of Subjects Who Successfully Consume a Wheat Protein Oral Food Challenge | 3 Participants |