Food Hypersensitivity, Hypersensitivity, Immediate Hypersensitivity
Conditions
Keywords
Egg Allergy, Egg Oral Immunotherapy (OIT), Food Allergy
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.
Interventions
Egg white solid powder
DRUGControl Group
Placebo for egg white solid
Sponsors
Consortium of Food Allergy Research
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg | At the 2 year time point; Egg OIT participants must be approximately 4-6 weeks post-discontinuation of therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid | Following the blinded desensitization phase at approximately Week 44 | 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. |
| Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation | Initial day of dosing | 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. |
| Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg | Following the blinded desensitization phase at approximately Week 44 | 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. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline through the 2-year primary endpoint | 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. |
| Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid | 4 years (48 months) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at five university-based medical centers in the United States (Mt. Sinai School of Medicine, Johns Hopkins University, Duke University, National Jewish Medical Center, University of Arkansas Children's Hospital) from July 2007 to December 2008.
Participants by arm
| Arm | Count |
|---|---|
| Egg Oral Immunotherapy (OIT) Subjects ingest egg white solid (EWS) on Visit 1 (initial day dose escalation up to 50 mg), followed by a build-up phase (escalating daily egg doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects are on a maximally tolerated daily egg dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects are given a 5 gm Oral Food Challenge (OFC) using EWS to identify desensitized \[1\] subjects. Subjects/study staff are unblinded following this OFC and either continue on their egg OIT maintenance dose of 2 gm/day or are allowed to attempt escalation up to 2 gm/day for the remainder of the study (1-3 years). A 10 gm OFC to identify desensitized \[1\] subjects occurs at specified intervals under prescribed conditions (yrs 2 - 4). Subjects who pass this 1st 10 gm OFC stop study therapy for 4-6 wks, then have a 2nd 10 gm OFC. Subjects that pass this 2nd 10 gm OFC are considered tolerant \[2\], stop EWS dosing and add egg to their diet. | 40 |
| Placebo Subjects ingest placebo (cornstarch) during Visit 1 (initial day of dose escalation up to 50 mg), followed by a build-up phase (escalating daily placebo doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects were on a maximally tolerated daily placebo dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects were given a 5 gm Oral Food Challenge (OFC) using egg white solid to identify desensitized \[1\] subjects. Subjects/study staff were unblinded following this initial 5 gm OFC. After unblinding, subjects discontinued further placebo dosing and continued on an egg-restricted diet. A 10 gm OFC was administered under prescribed conditions to subjects if their egg-specific serum IgE level was below 2 kUA/L. They were followed in the study up to 2 years. \[1\] Desensitized: Subject does not react to egg during OFC while taking daily doses of therapy. \[2\] Tolerant: Subject does not react to egg during OFC 4-6 wks after abstinence from egg consumption. | 15 |
| Total | 55 |
Baseline characteristics
| Characteristic | Egg Oral Immunotherapy (OIT) | Placebo | Total |
|---|---|---|---|
| Age at Initial Egg Allergic Reaction | 2.3 years STANDARD_DEVIATION 2.1 | 1.3 years STANDARD_DEVIATION 1.4 | 2.0 years STANDARD_DEVIATION 2 |
| Age, Categorical <=18 years | 40 Participants | 15 Participants | 55 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 7.1 years STANDARD_DEVIATION 1.6 | 7.1 years STANDARD_DEVIATION 1.6 | 7.1 years STANDARD_DEVIATION 1.6 |
| Atopic Dermatitis Total Score | 3.1 Scores on a scale STANDARD_DEVIATION 2.5 | 3.0 Scores on a scale STANDARD_DEVIATION 2.8 | 3.1 Scores on a scale STANDARD_DEVIATION 2.5 |
| Egg IgE | 32.9 kUA/L STANDARD_DEVIATION 54.7 | 32.1 kUA/L STANDARD_DEVIATION 27.3 | 32.7 kUA/L STANDARD_DEVIATION 48.5 |
| Egg Skin Prick Test Score | 11.8 mm STANDARD_DEVIATION 5.7 | 12.8 mm STANDARD_DEVIATION 4.3 | 12.1 mm STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 14 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 34 Participants | 14 Participants | 48 Participants |
| Region of Enrollment United States | 40 participants | 15 participants | 55 participants |
| Sex: Female, Male Female | 15 Participants | 6 Participants | 21 Participants |
| Sex: Female, Male Male | 25 Participants | 9 Participants | 34 Participants |
| Total IgE | 1378.7 kU/L STANDARD_DEVIATION 1728.6 | 1464.7 kU/L STANDARD_DEVIATION 1182.7 | 1402.1 kU/L STANDARD_DEVIATION 1588.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 40 | 15 / 15 | 26 / 36 |
| serious Total, serious adverse events | 3 / 40 | 0 / 15 | 1 / 36 |
Outcome results
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.
Time frame: At the 2 year time point; Egg OIT participants must be approximately 4-6 weeks post-discontinuation of therapy
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg | 27.5 percentage of participants |
| Placebo | Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg | 0 percentage of participants |
Comparison: Number of participants who successfully consumed 10,000 mg of egg white solid was compared using Barnard's statistic with the null hypothesis that there was no difference between treatment groups.p-value: 0.02595% CI: [4.3, 43.9]Barnard's statistic
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.
Time frame: Baseline through the 2-year primary endpoint
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Number of Participants With Serious Adverse Events (SAEs) | 3 participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) | 0 participants |
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.
Time frame: 4 years (48 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid | 52.5 percentage of participants |
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.
Time frame: Following the blinded desensitization phase at approximately Week 44
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg | 45.0 percentage of participants |
| Placebo | Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg | 80.0 percentage of participants |
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.
Time frame: Following the blinded desensitization phase at approximately Week 44
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid | 55.0 percentage of participants |
| Placebo | Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid | 0.0 percentage of participants |
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.
Time frame: Initial day of dosing
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Egg Oral Immunotherapy (OIT) | Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation | 22.5 percentage of participants |
| Placebo | Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation | 86.7 percentage of participants |