Peanut Allergic Subjects
Conditions
Keywords
Peanut Allergy, Anaphylaxis, Desensitization, Food Allergy, Oral Immunotherapy
Brief summary
Many children who are allergic to peanuts do not outgrow their allergy and have very severe allergic reactions called anaphylaxis. Symptoms of anaphylaxis include difficulty breathing, decreased blood pressure, hives, and lip or throat swelling after exposure to an allergen. A severe allergic reaction can lead to death if not treated appropriately. The purpose of this study is to find out if there is a way to treat children with peanut allergy to help lower the risk of severe allergic reactions and also cause them to lose their allergy to peanuts. The approach that will used for this study is a process called desensitization. Oral immunotherapy involves eating gradually increasing amounts of a food over several months. This is a research study because at this time peanut oral immunotherapy (OIT) is investigational. Peanut OIT (study drug) is investigational because it is not currently approved for clinical use by the Food and Drug Administration. There are no alternative safe and effective treatments for peanut induced allergic reactions other than peanut avoidance and treatment with medications.
Detailed description
This is a phase I, open label study for the initial 12 month desensitization phase of peanut oral immunotherapy and a 2 year maintenance phase. Subjects will be recruited to determine the immune response during the administration of peanut OIT after the development of disease. Cohort will include children age 5-16 years who have peanut allergy. The study will require approximately 36 visits with 3 phases: screening phase (\ 2 months); build-up phase (weeks 1 year), followed by the maintenance phase (2 years). The primary objective of the OIT protocol is to desensitize subjects to peanut and this occurs over the first 12 months of the study (build-up phase). The first dose will be based on the amount at which the subject reacted during a double blind placebo controlled food challenge (DBPCFC). Thereafter, dose escalation would continue as outlined in the protocol for approximately 50 weeks until the maintenance dose of peanut protein (3900 mg) is reached. The maintenance phase will continue from the end of the build-up phase until approximately 24 months. During this phase, the subject will switch to a peanut equivalent dose for the maintenance phase. At the conclusion of the maintenance phase a DBPCFC will be done. Negative challenges will be confirmed by open challenge. DBPCFC will be done.
Interventions
BIOLOGICALPeanut Oral Immunotherapy (POIT)
The peanut protein is ingested in the form of peanut flour. Peanut flour will be given in small pre-measured soufflé cups containing the amount of peanut flour that needs to be eaten for one dose. One dose will be taken per day. Dosage of the peanut flour will begin with 1.8 mg of peanut protein during the initial visit or the lowest tolerated dose on initial challenge and increased every 2 during the build-up phase until the maintenance dose of peanut protein (3900 mg) is reached.
Sponsors
Baylor College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Age 5-16 years of either sex, any race, any ethnicity, weighing at least 18.3 kg at the time of the initial visit. * The presence of Immunoglobulin E (IgE) specific to peanuts (a positive skin prick test to peanuts (diameter of wheal \> 3.0 mm) and a positive in vitro IgE \[CAP-FEIA\] \> 7 kUA/L) measured within the past year. * Significant clinical symptoms occurring within 120 minutes after ingesting peanuts during an observed DBPCFC. Patients who have not had previous oral exposure to peanut will be observed for a longer duration of 150 minutes because they may demonstrate a delayed immune response, given the lack of prior peanut exposure. Also, patients with a history of prior anaphylaxis will be observed for 150 minutes. * Provide signed informed consent. * Ability to follow-up regularly for scheduled appointments. * Subjects will not be excluded if they are primarily Spanish speaking. * Females of childbearing potential must be willing to practice an acceptable form of birth control throughout the protocol. * Epinephrine injection training provided. Participant has current in-date epinephrine injector and parent/guardian demonstrates proper use
Exclusion criteria
* History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise (Cyanosis or SpO2 \< 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence) * Currently participating in a study using an investigational new drug. * Participation in any interventional study for the treatment of food allergy in the past 12 months or while participating in this study. * Poor control or persistent activation of atopic dermatitis. * Diagnosis of persistent asthma as defined by NHLBI criteria and currently being treated with daily doses of inhaled corticosteroids or requiring a rescue inhaler more than 2 days per week. * Inability to discontinue antihistamines for skin testing and Oral Food Challenges (OFCs). * Pregnant female. * Chronic medical condition requiring frequent use of oral steroids, chronic psychiatric illness or history of substance abuse. * Active eosinophilic esophagitis requiring medication therapy during the past 12 months. * Subjects with known oat or wheat allergy * Subjects currently on the build-up phase of environmental allergy immunotherapy injections * Live more than 175 miles away from Texas Children's Hospital located in the Medical Center.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Percentage of Patients Tolerating the 12-month DBPCFC | Month 12 after first dose of peanut flour | Patients underwent a build-up phase (month 0-12). The patients returned every 2 weeks during the build-up phase until the maintenance dose of 3900 mg was achieved. The 12-month double blind placebo controlled food challenge (DBPFC) was performed on achieving the maintenance dose. The primary objective was to determine the percentage of subjects tolerating a cumulative dose of 26255 mg of peanut flour with absence of clinical symptoms during the 12-month DBPCFC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Unresponsiveness After 1 Month of Treatment Discontinuation | Month 36 and 37 after first dose of peanut flour | To compare the change in dose tolerated after one month of abstaining from peanut to determine sustained unresponsiveness. The subjects underwent a DBPCFC at month 36 and month 37. The mean of the highest dose tolerated by the subjects was assessed at these two timepoints. |
Countries
United States
Participant flow
Recruitment details
Study recruitment began on 7/31/2014 and the last subject was recruited on 12/23/2016. Participants were recruited from the Food Allergy Program at Texas Children's Hospital and by referral from community physicians.
Pre-assignment details
Participants were brought in for a screening visit to assess for eligibility in the study. 28 subjects were seen for screening visit and 13 subjects were ineligible due to failure to complete food challenge (1), FEV1\<90% predicted on spirometry (4), Peanut IgE \< 7 kU/L (1), and were not interested due to time commitment (5), unable to tolerate initial dose (2).
Participants by arm
| Arm | Count |
|---|---|
| Peanut Oral Immunotherapy (POIT) Peanut Oral Immunotherapy (POIT): The peanut protein is ingested in the form of peanut flour. Peanut flour will be given in small pre-measured soufflé cups containing the amount of peanut flour that needs to be eaten for one dose. One dose will be taken per day. Dosage of the peanut flour will begin with 1.8 mg of peanut protein during the initial visit or the lowest tolerated dose on initial challenge and increased every 2 during the build-up phase until the maintenance dose of peanut protein (3900 mg) is reached. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Peanut Oral Immunotherapy (POIT) |
|---|---|
| Age, Continuous | 8.74 years STANDARD_DEVIATION 2.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Participants that Completed the Protocol Completed | 12 Participants |
| Number of Participants that Completed the Protocol Withdrawal | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Determine the Percentage of Patients Tolerating the 12-month DBPCFC
Patients underwent a build-up phase (month 0-12). The patients returned every 2 weeks during the build-up phase until the maintenance dose of 3900 mg was achieved. The 12-month double blind placebo controlled food challenge (DBPFC) was performed on achieving the maintenance dose. The primary objective was to determine the percentage of subjects tolerating a cumulative dose of 26255 mg of peanut flour with absence of clinical symptoms during the 12-month DBPCFC.
Time frame: Month 12 after first dose of peanut flour
Population: Three (3) subjects withdrew from the trial prior to maintenance phase. Only 12 subjects were analyzed for this objective.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Percentage of Subjects Who Tolerated 6000mg | Determine the Percentage of Patients Tolerating the 12-month DBPCFC | Tolerated | 2 Participants |
| Percentage of Subjects Who Tolerated 6000mg | Determine the Percentage of Patients Tolerating the 12-month DBPCFC | Did not tolerate | 10 Participants |
Secondary
Sustained Unresponsiveness After 1 Month of Treatment Discontinuation
To compare the change in dose tolerated after one month of abstaining from peanut to determine sustained unresponsiveness. The subjects underwent a DBPCFC at month 36 and month 37. The mean of the highest dose tolerated by the subjects was assessed at these two timepoints.
Time frame: Month 36 and 37 after first dose of peanut flour
Population: Nine (9) patients did not complete the food challenge after one month of abstaining from peanut. Six (6) patients were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Percentage of Subjects Who Tolerated 6000mg | Sustained Unresponsiveness After 1 Month of Treatment Discontinuation | 37 month challenge | 1010.88 mg | Standard Error 835.33 |
| Percentage of Subjects Who Tolerated 6000mg | Sustained Unresponsiveness After 1 Month of Treatment Discontinuation | 36 month challenge | 2736.67 mg | Standard Error 854.7 |