Food Hypersensitivity
Conditions
Keywords
Peanut Allergy, Sublingual immunotherapy
Brief summary
The specific aim of this study is to determine if peanut allergen-specific SLIT will cause clinical desensitization and tolerance to develop in peanut-allergic young children.
Detailed description
In spite of increased recognition and understanding of food allergies, food-induced anaphylaxis remains the single most common cause of anaphylaxis seen in hospital emergency departments, accounting for about one third of anaphylaxis cases seen. It is estimated that about 30,000 food-induced anaphylactic events are seen in U.S. emergency departments each year and that about 200 fatal cases occur in the U.S. each year. Either peanuts or tree nuts cause more than 80% of these reactions. No treatments are available and avoidance is the only approved intervention. The goal of this study is to investigate peanut sublingual immunotherapy (SLIT) as a treatment for children with peanut allergy. This study is primarily designed to evaluate the efficacy and safety of peanut SLIT compared to placebo after 12 months. Secondarily, the study is designed to evaluate the efficacy of extended maintenance dosing of peanut SLIT in inducing lasting tolerance after discontinuation of the peanut SLIT. Mechanistic studies will be completed concurrently as exploratory endpoints to understand changes in the allergic immune response related to peanut SLIT.
Interventions
DRUGPeanut SLIT
Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.
DRUGPlacebo SLIT
Liquid glycerin without peanut which are dosed under the tongue.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
For the initial 12 months of the study, subjects were blinded to receive either peanut SLIT or placebo. After unblinding, subjects on placebo are crossed over to receive open-label peanut SLIT. They underwent an identical dosing protocol as those that were initially randomized to active treatment. After 12 months of peanut SLIT dosing, whether initially randomized to active or crossed over from placebo, all subjects remained part of an open-label extended maintenance phase for the duration of the study (total peanut SLIT dosing 36-60 months) 2 additional cohorts were included in the protocol. One cohort, called the Early Unblinded Peanut SLIT cohort, was unblinded prior to the scheduled 12 month time point for pharmacy safety concerns. The second cohort, called the Pilot Peanut SLIT Rollover cohort involved subjects from the prior pilot study (NCT00429429) who were added to the study through an amendment and received open-label peanut SLIT.
Eligibility
Sex/Gender
ALL
Age
1 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Peanut IgE \> 7kU/L (\> 2kU/L for children aged 2 years and under) AND * History of significant clinical symptoms within 60 minutes after the ingestion of peanuts.
Exclusion criteria
* History of severe life-threatening anaphylaxis to peanut, OR * Medical history that would prevent a DBPCFC to peanut, OR * Subjects with wheat or oat allergy (which are used in the placebo), OR * Unable to cooperate with challenge procedures, OR * Unable to be reached by telephone for follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | 12 months | Upon completion of 12 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 2500 mg peanut protein DBPCFC without developing symptoms after 12 months of peanut SLIT therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing | 36-60 months | Upon completion of 36-60 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. Peanut SLIT therapy was then discontinued for 2-4 weeks to assess for persistence of the desensitization response called sustained unresponsiveness (SU). The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5000 mg peanut protein DBPCFC without developing symptoms 2-4 weeks after discontinuing peanut SLIT therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Blinded Peanut SLIT Blinded subjects who received peanut sublingual drops) at the beginning of the study. | 14 |
| Blinded Placebo SLIT Blinded subjects who receive placebo (glycerin sublingual drops) at the beginning of the study.
Placebo SLIT: Liquid glycerin without peanut which are dosed under the tongue. | 15 |
| Early Unblinded Peanut SLIT Subjects who were unblinded prematurely during the blinded phase of the study and then re-enrolled as an open label cohort. | 27 |
| Pilot Peanut SLIT Rollover Cohort Subjects from the original phase 1 study of peanut SLIT (NCT00429429) who were rolled over into the current protocol as an open label peanut SLIT cohort. | 4 |
| Total | 60 |
Baseline characteristics
| Characteristic | Blinded Peanut SLIT | Blinded Placebo SLIT | Early Unblinded Peanut SLIT | Pilot Peanut SLIT Rollover Cohort | Total |
|---|---|---|---|---|---|
| Age, Continuous | 6.0 years | 6.6 years | 6.0 years | 15.6 years | 6.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 15 Participants | 27 Participants | 4 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 24 Participants | 3 Participants | 54 Participants |
| Region of Enrollment United States | 14 participants | 15 participants | 27 participants | 4 participants | 60 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 6 Participants | 0 Participants | 18 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 21 Participants | 4 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 15 | 0 / 29 | 0 / 27 | 0 / 4 |
| other Total, other adverse events | 10 / 14 | 12 / 15 | 21 / 29 | 19 / 27 | 3 / 4 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 | 0 / 29 | 0 / 27 | 0 / 4 |
Outcome results
Primary
Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing
Upon completion of 12 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 2500 mg peanut protein DBPCFC without developing symptoms after 12 months of peanut SLIT therapy.
Time frame: 12 months
Population: Interim analysis in 7/2010 showed statistically significant difference in peanut tolerated during oral food challenge (OFC) by active treatment vs placebo (1710mg vs 85mg). Further OFCs for those on placebo was considered more risk than benefit thus were discontinued resulting in subsequent patients being unblinded after 12 months without an OFC
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Blinded Peanut SLIT | Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | 45.5 percentage of participants |
| Blinded Placebo SLIT | Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | 0 percentage of participants |
| Early Unblinded Peanut SLIT | Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | 11.8 percentage of participants |
| Pilot Peanut SLIT Rollover Cohort | Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | 66.7 percentage of participants |
Secondary
Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing
Upon completion of 36-60 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. Peanut SLIT therapy was then discontinued for 2-4 weeks to assess for persistence of the desensitization response called sustained unresponsiveness (SU). The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5000 mg peanut protein DBPCFC without developing symptoms 2-4 weeks after discontinuing peanut SLIT therapy.
Time frame: 36-60 months
Population: Although the 12 month OFC was discontinued beginning in 7/2010, all subjects reaching the end of study (36-60 months of treatment) underwent an OFC resulting in more patients performing the end of study OFC than the 12 month OFC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Blinded Peanut SLIT | Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing | 26.1 percentage of participants |
| Blinded Placebo SLIT | Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing | 28.6 percentage of participants |
| Early Unblinded Peanut SLIT | Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing | 0 percentage of participants |