Food Allergy
Conditions
Keywords
Egg Allergy, Egg Oral Immunotherapy, Food Allergy
Brief summary
The purpose of this study is to compare Baked Egg vs. Egg Oral Immunotherapy for inducing sustained unresponsiveness to egg exposure in children.
Detailed description
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.
Interventions
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.
DRUGBaked Egg
Predetermined food substances with known amounts of Baked Egg (egg protein) with standardized dosing/consumption instructions.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Consortium of Food Allergy Research
Hugh A Sampson, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 16 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Study recruitment began in July 2013 and accrual closed in August 2015.
Participants by arm
| Arm | Count |
|---|---|
| Baked Egg Randomized Subjects who passed a baked egg oral food challenge (OFC) at baseline were randomized to receive baked egg in the form of home-baked goods and safe commercial products with up to four oral food challenges as directed by the protocol.
Baked Egg: Predetermined food substances with known amounts of Baked Egg (egg protein) with standardized dosing/consumption instructions. | 27 |
| Egg OIT Randomized Subjects who passed a baked egg oral food challenge (OFC) at baseline were randomized to receive egg oral immunotherapy (OIT) in the form of egg white solid with up to four oral food challenges as directed by protocol.
Egg Oral Immunotherapy: 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. | 23 |
| Egg OIT Assigned Subjects who failed a baked egg oral food challenge (OFC) at baseline were assigned to receive egg oral immunotherapy (OIT) in the form of egg white solid with up to four oral food challenges as directed by protocol.
Egg Oral Immunotherapy: 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. | 39 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Developed Eosinophilic Esophagitis (EoE) | 1 | 0 | 0 |
| Overall Study | Dosing Symptoms | 1 | 2 | 6 |
| Overall Study | Non-compliance | 1 | 1 | 0 |
| Overall Study | Refused SU OFC | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 0 | 0 |
| Overall Study | Withdrew prior to treatment | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Baked Egg Randomized | Total | Egg OIT Assigned | Egg OIT Randomized |
|---|---|---|---|---|
| Age, Continuous | 7.2 years STANDARD_DEVIATION 3 | 8.4 years STANDARD_DEVIATION 2.8 | 8.8 years STANDARD_DEVIATION 2.4 | 9.1 years STANDARD_DEVIATION 3.1 |
| Allergic GI Disease | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Allergic Rhinitis | 24 Participants | 73 Participants | 31 Participants | 18 Participants |
| Asthma Severity History Mild intermittent | 16 Participants | 50 Participants | 24 Participants | 10 Participants |
| Asthma Severity History Mild persistent | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Asthma Severity History Moderate persistent | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Asthma Severity History No History | 9 Participants | 32 Participants | 13 Participants | 10 Participants |
| Atopic Dermatitis History | 18 Participants | 55 Participants | 24 Participants | 13 Participants |
| Atopic Dermatitis Score | 0.0 units on a scale | 0.0 units on a scale | 0.0 units on a scale | 0.0 units on a scale |
| Baseline Cockroach SPT | 0.00 mms | 0.00 mms | 0.00 mms | 0.00 mms |
| Baseline Egg IgE | 9.77 kUA/L | 15.60 kUA/L | 26.25 kUA/L | 12.30 kUA/L |
| Baseline Egg %IgE | 1.86 % IgE | 2.13 % IgE | 3.06 % IgE | 1.80 % IgE |
| Baseline Egg IgG4 | 0.84 mgA/L | 0.64 mgA/L | 0.28 mgA/L | 0.81 mgA/L |
| Baseline Egg Skin Prick Test (SPT) | 7.50 mms | 11.00 mms | 12.00 mms | 11.00 mms |
| Baseline Grass SPT | 4.50 mms | 2.50 mms | 2.50 mms | 0.00 mms |
| Baseline Milk SPT | 1.00 mms | 2.50 mms | 3.50 mms | 3.00 mms |
| Baseline Mold SPT | 0.50 mms | 0.00 mms | 0.00 mms | 1.00 mms |
| Baseline Ovalbumin IgE | 5.53 kUA/L | 8.88 kUA/L | 16.10 kUA/L | 5.85 kUA/L |
| Baseline Ovalbumin IgG4 | 0.64 mgA/L | 0.49 mgA/L | 0.33 mgA/L | 0.53 mgA/L |
| Baseline Ovomucoid IgE | 6.94 kUA/L | 9.76 kUA/L | 16.40 kUA/L | 6.93 kUA/L |
| Baseline Ovomucoid IgG4 | 0.25 mgA/L | 0.11 mgA/L | 0.09 mgA/L | 0.15 mgA/L |
| Baseline Peanut SPT | 10.50 mms | 11.00 mms | 10.50 mms | 11.00 mms |
| Baseline Ratio IgG4/IgE | 24.94 ratio | 11.18 ratio | 5.01 ratio | 25.75 ratio |
| Baseline Total IgE | 809.00 kUA/L | 885.50 kUA/L | 960.00 kUA/L | 873.00 kUA/L |
| Baseline Tree SPT | 2.50 mms | 3.50 mms | 3.00 mms | 4.50 mms |
| Baseline Weed SPT | 1.50 mms | 0.00 mms | 0.00 mms | 0.00 mms |
| Other Food Allergy History No/Unknown | 1 Participants | 12 Participants | 8 Participants | 3 Participants |
| Other Food Allergy History Yes | 26 Participants | 77 Participants | 31 Participants | 20 Participants |
| Race/Ethnicity, Customized Hispanic or Latino origin | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-Hispanic or Non-Latino origin | 25 Participants | 87 Participants | 39 Participants | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 6 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 72 Participants | 31 Participants | 18 Participants |
| Sex: Female, Male Female | 12 Participants | 32 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 15 Participants | 57 Participants | 25 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 23 | 0 / 39 |
| other Total, other adverse events | 27 / 27 | 23 / 23 | 39 / 39 |
| serious Total, serious adverse events | 0 / 27 | 0 / 23 | 1 / 39 |
Outcome results
Primary
Sustained Unresponsiveness to Egg Consumption at 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.
Time frame: 2 Years
Population: All treated participants were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Baked Egg Randomized | Sustained Unresponsiveness to Egg Consumption at 2 Years. | 3 Participants |
| Egg OIT Randomized | Sustained Unresponsiveness to Egg Consumption at 2 Years. | 10 Participants |
| Egg OIT Assigned | Sustained Unresponsiveness to Egg Consumption at 2 Years. | 7 Participants |
Comparison: % participants passed Year 2 SU OFC: Baked vs. Egg OIT-Randomizedp-value: 0.00995% CI: [8.9, 55.8]Barnard's Exact Test
Comparison: % participants passed Year 2 SU OFC: Egg OIT-Randomized vs. Egg OIT-Assignedp-value: 0.03195% CI: [2, 49.1]Barnard's Exact Test
Secondary
Desensitization to >= 4.444 Grams Egg White Solid.
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.
Time frame: 1 Year and 2 Years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Baked Egg Randomized | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 1 | 8 Participants |
| Baked Egg Randomized | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 2 | 6 Participants |
| Egg OIT Randomized | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 1 | 17 Participants |
| Egg OIT Randomized | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 2 | 20 Participants |
| Egg OIT Assigned | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 1 | 22 Participants |
| Egg OIT Assigned | Desensitization to >= 4.444 Grams Egg White Solid. | Desensitized Success at Year 2 | 27 Participants |
Comparison: % participants desensitized to \>=4444 mg at Year 2 OFC: Baked vs. Egg OIT-Randomizedp-value: <0.000195% CI: [43.9, 85.6]Barnard's Exact Test
Comparison: % participants desensitized to \>=4444 mg at Year 2 OFC: Egg OIT-Randomized vs. Egg OIT-Assignedp-value: 0.15195% CI: [-2.3, 37.7]Barnard's Exact Test
Comparison: % participants desensitized to \>=4444 mg at Year 1 OFC: Baked vs. Egg OIT-Randomizedp-value: 0.00295% CI: [19.4, 69.2]Barnard's Exact Test
Comparison: % participants desensitized to \>=4444 mg at Year 1 OFC: Egg OIT-Randomized vs. Egg OIT-Assignedp-value: 0.18195% CI: [-6.3, 41.3]Barnard's Exact Test
Secondary
Incidence of All Serious Adverse Events
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.
Time frame: up to 3 years
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Baked Egg Randomized | Incidence of All Serious Adverse Events | 0 Participants |
| Egg OIT Randomized | Incidence of All Serious Adverse Events | 0 Participants |
| Egg OIT Assigned | Incidence of All Serious Adverse Events | 1 Participants |
Secondary
Number of Participants With Unrestricted Consumption of Unbaked Egg
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.
Time frame: 3 years after randomization
Population: Participants who completed the long term follow-up questionnaire 3 years after randomization are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Baked Egg Randomized | Number of Participants With Unrestricted Consumption of Unbaked Egg | 4 Participants |
| Egg OIT Randomized | Number of Participants With Unrestricted Consumption of Unbaked Egg | 14 Participants |
| Egg OIT Assigned | Number of Participants With Unrestricted Consumption of Unbaked Egg | 12 Participants |
Comparison: % participants with unrestricted consumption of unbaked (concentrated) egg 3 years after randomization: Baked vs. Egg OIT-Randomizedp-value: 0.00395% CI: [-78.4, -21.9]Barnard's Exact Test
Comparison: % participants with unrestricted consumption of unbaked (concentrated) egg 3 years after randomization: Egg OIT-Randomized vs. Egg OIT-Assignedp-value: 0.02395% CI: [7.2, 60.1]Barnard's Exact Test
Other Pre-specified
Changes in Egg-specific Mechanistic Measures and Skin Prick Test Results.
Changes in egg-specific IgE and IgG4, changes in SPT mean wheal diameters, basophil reactivity, Th2 and Treg values.
Time frame: 2 Years
Population: Data not reported because these are for tertiary objectives that are exploratory.