Eczema, Egg Allergy, Food Allergy, Hypersensitivity
Conditions
Keywords
Peanut
Brief summary
ITN049AD (LEAP-On) Study is a continuation of the ITN032AD LEAP Study (NCT00329784). Peanut Allergy, a recognized public health concern, is a common and potentially life-threatening food allergy for which there is no treatment. ITN032AD (LEAP) Study evaluated whether early exposure to peanut promotes tolerance and provides protection from developing peanut allergy in children who are allergic to eggs or who have severe eczema. ITN049AD (LEAP-On) Study will evaluate persistent tolerance to peanut by assessing the effect of twelve months of cessation of peanut consumption in LEAP Study participants who consumed peanut and those who avoided peanut over the previous five years.
Detailed description
This is a two-sample comparison employing all available study participants in both arms of the LEAP (NCT00329784) study at visit 72. After obtaining informed consent, LEAP participants who are evaluable for peanut allergy at age 60 months (V60) will be enrolled into this study, the LEAP-On (NCT01366846) Study. All LEAP-On participants will avoid peanut for an additional 12 months regardless of their previous allocation to the LEAP Study consumption arm (Group A) or the LEAP Study avoidance arm (Group B). At V72, after 12 months of this new intervention, all participants will have skin prick testing (SPT), specific IgE and a repeat oral challenge to peanut to determine the frequency of peanut allergy in both groups. The LEAP Study decision table will be used to determine the presence of peanut allergy. Briefly, peanut allergy will be based on the presence of a positive oral peanut challenge with objective signs of allergy. Tolerance will be established on the basis of a negative oral peanut challenge (tolerating 5 g of peanut protein in the absence of symptoms). For participants who do not have an oral challenge or an oral challenge at V72 with a determinate outcome, the following criteria will be used to determine their outcome at V72: * If the participant is tolerant and has an IgE \> 0.1 and/or SPT \> 0 mm at V60, the participant will be considered non-evaluable and will not be included in the analysis. * For all other participants, the V60 outcome will be applied to the V72 outcome (last observation carried forward). Predictive values of peanut-specific IgE and/or SPT will not be used in the LEAP-On study because participants in the peanut consumption arm in the LEAP study are tolerating peanuts despite having high IgE and/or SPT.
Interventions
OTHERAvoidance of peanut
All participants will be assigned to peanut avoidance as per United Kingdom (UK) public health recommendations and will avoid exposure to peanut protein during the study until the last study visit when they will receive the Oral Food Challenge.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* All LEAP Study participants who are evaluable for peanut allergy at year 5 by LEAP (ClinicalTrials.gov ID NCT00329784) Study criteria. * Parent or guardian willing to provide informed consent.
Exclusion criteria
* Unable or unwilling to comply with study intervention and procedures. * Participation in other food allergy intervention trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | 72 months | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to not have peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. |
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group | 72 months | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. |
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | 72 months | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have peanut allergy. |
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population | 72 months | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group | 60 months and 72 months | At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. |
| Number of Peanut Avoidance After Peanut Consumption Group Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within in the Per Protocol Population | 60 months and 72 months | At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. |
Countries
United Kingdom
Participant flow
Recruitment details
From among those who completed the LEAP study (protocol ID ITN032AD, ClinicalTrials.gov ID NCT00329784), 556 subjects were recruited between 26 May 2011 and 6 June 2014 at Evelina Children's Hospital in London, UK.
Pre-assignment details
In the LEAP trial, participants were stratified into strata based on a peanut allergen skin prick test (SPT). Participants were either SPT negative (0mm wheal) or SPT positive (1-4 mm wheal). Participants were then randomized into treatment groups within each stratum. This configuration was preserved in LEAP-On (this trial)
Participants by arm
| Arm | Count |
|---|---|
| Negative Stratum - Peanut Avoidance Group Participants who had a negative response to a skin prick test for peanut allergen (no measurable wheal) and were then randomized to the peanut avoidance group. Participants were instructed to avoid exposure to peanut protein during study participation. | 235 |
| Negative Stratum - Peanut Consumption Group Participants who had a negative response to a skin prick test for peanut allergen (no measurable wheal) and were then randomized to the peanut consumption group. Participants were fed at least 2 g of peanut protein 3 times per week (a total of 6g). The preferred peanut source was Bamba (a peanut snack), although peanut butter was an acceptable substitute. After age 3, participants were allowed to eat whole peanuts. | 228 |
| Positive Stratum - Peanut Avoidance Group Participants who had a positive response to a skin prick test for peanut allergen (a wheal measuring between 1 and 4 mm) and were then randomized to the peanut avoidance group. Participants were instructed to avoid exposure to peanut protein during study participation. | 47 |
| Positive Stratum - Peanut Consumption Group Participants who had a positive response to a skin prick test for peanut allergen (a wheal measuring between 1 and 4 mm) and were then randomized to the peanut consumption group. Participants were fed at least 2 g of peanut protein 3 times per week (a total of 6g). The preferred peanut source was Bamba (a peanut snack), although peanut butter was an acceptable substitute. After age 3, participants were allowed to eat whole peanuts. | 46 |
| Total | 556 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Communication Difficulties | 1 | 4 | 0 | 1 |
| Overall Study | Scheduling Conflicts | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Negative Stratum - Peanut Avoidance Group | Negative Stratum - Peanut Consumption Group | Positive Stratum - Peanut Avoidance Group | Positive Stratum - Peanut Consumption Group | Total |
|---|---|---|---|---|---|
| Age, Customized Age in Months | 61.0 Months STANDARD_DEVIATION 3.44 | 61.7 Months STANDARD_DEVIATION 4.19 | 60.6 Months STANDARD_DEVIATION 3.76 | 61.4 Months STANDARD_DEVIATION 4.98 | 61.3 Months STANDARD_DEVIATION 3.93 |
| Region of Enrollment United Kingdom | 235 participants | 228 participants | 47 participants | 46 participants | 556 participants |
| Sex: Female, Male Female | 85 Participants | 102 Participants | 14 Participants | 18 Participants | 219 Participants |
| Sex: Female, Male Male | 150 Participants | 126 Participants | 33 Participants | 28 Participants | 337 Participants |
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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 206 / 235 | 182 / 228 | 45 / 47 | 38 / 46 |
| serious Total, serious adverse events | 12 / 235 | 7 / 228 | 3 / 47 | 2 / 46 |
Outcome results
Primary
Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum
At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to not have peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA.
Time frame: 72 months
Population: Intent-to-treat with available data at 72 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | 34 Participants |
| Negative Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | 7 Participants |
| Positive Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | 18 Participants |
| Positive Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | 6 Participants |
Comparison: Comparison of the percentage of subjects with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Avoidance After Peanut Consumption Group within the SPT-negative stratum.p-value: <0.001Chi-squared
Comparison: Comparison of the percentage of subjects with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Avoidance After Peanut Consumption Group within the SPT-positive stratum.p-value: 0.004Chi-squared
Primary
Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population
At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have peanut allergy.
Time frame: 72 months
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | 34 Participants |
| Negative Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | 7 Participants |
| Positive Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | 18 Participants |
| Positive Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | 6 Participants |
Comparison: Comparison of the percentage of subjects with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Avoidance After Peanut Consumption Group within the SPT-negative stratum.p-value: <0.001Chi-squared
Comparison: Comparison of the percentage of subjects with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Avoidance After Peanut Consumption Group within the SPT-positive stratum.p-value: 0.027Chi-squared
Primary
Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group
At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA.
Time frame: 72 months
Population: Intent-to-treat with available data at 72 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group | 52 Participants |
| Negative Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group | 13 Participants |
Comparison: Comparison of the percentage of participants with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Consumption Group across both the SPT-negative and SPT-positive strata.p-value: <0.001Chi-squared
Primary
Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population
At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA.
Time frame: 72 months
Population: Per Protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population | 52 Participants |
| Negative Stratum - Peanut Consumption Group | Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population | 13 Participants |
Comparison: Comparison of the percentage of subjects with peanut allergy in the Continued Peanut Avoidance Group to that of the Peanut Avoidance After Peanut Consumption Group across both the SPT-negative and SPT-positive strata.p-value: <0.001Chi-squared
Secondary
Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group
At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA.
Time frame: 60 months and 72 months
Population: Intent-to-treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group | Month 60 | 10 Participants |
| Negative Stratum - Peanut Avoidance Group | Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group | Month 72 | 13 Participants |
Comparison: Comparison of the percentage of subjects with peanut allergy in the Peanut Avoidance After Peanut Consumption Group at month 60 to that of the Peanut Avoidance After Peanut Consumption Group at month 72 across both the SPT-negative and SPT-positive strata.p-value: 0.25Exact McNemar
Secondary
Number of Peanut Avoidance After Peanut Consumption Group Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within in the Per Protocol Population
At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA.
Time frame: 60 months and 72 months
Population: Per Protocol
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Negative Stratum - Peanut Avoidance Group | Number of Peanut Avoidance After Peanut Consumption Group Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within in the Per Protocol Population | Month 60 | 10 Participants |
| Negative Stratum - Peanut Avoidance Group | Number of Peanut Avoidance After Peanut Consumption Group Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within in the Per Protocol Population | Month 72 | 13 Participants |
Comparison: Comparison of the percentage of subjects with peanut allergy in the Peanut Avoidance After Peanut Consumption Group at month 60 to that of the Peanut Avoidance After Peanut Consumption Group at month 72 across both the SPT-negative and SPT-positive strata.p-value: 0.25Exact McNemar