Peanut Hypersensitivity
Conditions
Keywords
Peanut Allergy
Brief summary
Peanut allergy is known to cause severe anaphylactic reactions.The goal of this proposal is to produce a new treatment that would benefit subjects who have peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance).
Detailed description
Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies it tends to be more persistent and also its prevalence seems to be rising. Currently there is no proven treatment other than strict avoidance. We are attempting to decrease the risk of anaphylaxis on accidental ingestion by desensitizing subjects to peanut using peanut oral immunotherapy (OIT). We are also studying the effect of peanut OIT on the peanut specific immune response to determine if tolerance to peanut protein will develop. Children ages one to six years of age with peanut allergy will be randomized to peanut OIT or placebo (active subjects). Thirty subjects will also be recruited as controls. These subjects will not receive any peanut or placebo but only have skin prick testing and lab work in addition to a history and physical exam. Active subjects will undergo a modified rush immunotherapy on the first day and then increase the doses at least every two weeks up to a maintenance dose of 4 grams (equivalent to about 13 peanuts). Doses will be taken daily at home except for dose increases which will be done on the research unit. Outcome variables of interest include response to double-blind placebo controlled food challenge, skin prick testing, peanut specific IgE, and adverse events. These results will be compared between the start and end of peanut OIT using appropriate statistical analysis.
Interventions
DRUGPeanut OIT
Peanut flour that is orally ingested in a graded fashion.
DRUGPlacebo
Oat flour used as a placebo that is orally ingested a graded fashion
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
* Age 1- 6 years all of either sex, any race, any ethnicity at the time of the initial visit * The presence of 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 * A history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts * Provide signed informed consent
Exclusion criteria
* History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise (Cyanosis or oxygen saturation \< 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 * Subjects with a known wheat food allergy will be excluded because of cross contamination of oat with wheat * Poor control or persistent activation of atopic dermatitis * Moderate to severe persistent asthma * Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines * Inability to discontinue antihistamines for skin testing and oral food challenges (OFCs)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Tolerance as Defined by a Negative DBPCFC 4 Weeks After Discontinuation of Peanut OIT Therapy. | 61 months for those randomized to active treatment and 73 months for those randomized to placebo for the initial 12 months of therapy | Upon completion of 60 months of peanut OIT treatment, subjects discontinued peanut OIT for 4 weeks. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms 4 weeks after discontinuing peanut OIT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut | first day of peanut OIT dosing | The first day of peanut OIT dosing involved multiple increasing doses of peanut flour in what was called an initial escalation day up to a maximum dose of 6 mg of peanut protein. The secondary outcome measure assessed the percentage of subjects were successfully able to reach this 6 mg dose. |
| The Percentage of Subjects Achieving Full Desensitization as Defined by a Negative DBPCFC After 60 Months of Peanut OIT Therapy. | 60 months for those randomized to active treatment and 72 months for those randomized to placebo for the initial 12 months of therapy | Upon completion of 60 months of peanut OIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCPFC) to assess desensitization. The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms after completing peanut OIT therapy. |
| The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study | approximately 40 weeks (10 months) | During the desensitization phase of the study, subjects under go an initial day escalation up to a maximum of 6 mg of peanut protein. They then undergo biweekly dose escalation over approximately 10 months up to a maximum dose of 4000 mg of peanut protein. This outcome reports the percentage of subjects that achieve this. |
| Incidence of All Serious Adverse Events During the Study | 61 months for those randomized to active peanut OIT and 73 months for those randomized to placebo for the initial 12 months of the study. | All serious adverse events during the blinded and open-label phases of the study were recorded and reported as a safety outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Blinded Phase-Peanut OIT Subjects randomized over the initial 44+ weeks to receive active treatment with peanut OIT.
Peanut OIT: Peanut flour that is orally ingested in a graded fashion. | 10 |
| Blinded Phase-Placebo Subjects randomized over the first 44+ weeks to receive placebo in the form of oat flour.
Placebo: Oat flour used as a placebo that is orally ingested a graded fashion | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Blinded Phase-Peanut OIT | Blinded Phase-Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 6 Participants | 16 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 | 5.1 years | 4.8 years | 5.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 6 Participants | 16 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 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 | 8 Participants | 4 Participants | 12 Participants |
| Region of Enrollment United States | 10 participants | 6 participants | 16 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 15 |
| other Total, other adverse events | 10 / 10 | 4 / 6 | 15 / 15 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 15 |
Outcome results
Primary
Percentage of Subjects Achieving Tolerance as Defined by a Negative DBPCFC 4 Weeks After Discontinuation of Peanut OIT Therapy.
Upon completion of 60 months of peanut OIT treatment, subjects discontinued peanut OIT for 4 weeks. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms 4 weeks after discontinuing peanut OIT.
Time frame: 61 months for those randomized to active treatment and 73 months for those randomized to placebo for the initial 12 months of therapy
Population: Subjects completing 60 months of OIT treatment, then passing the DBPCFC on the last day of treatment, then completing the DBPCFC after 1 month off of treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Phase-Peanut OIT | Percentage of Subjects Achieving Tolerance as Defined by a Negative DBPCFC 4 Weeks After Discontinuation of Peanut OIT Therapy. | 89 percentage of participants |
Secondary
Incidence of All Serious Adverse Events During the Study
All serious adverse events during the blinded and open-label phases of the study were recorded and reported as a safety outcome.
Time frame: 61 months for those randomized to active peanut OIT and 73 months for those randomized to placebo for the initial 12 months of the study.
Population: The initial 10-11 months of the study were blinded. After unblinding, subjects completing the blinded phase continued on open label peanut OIT for the duration of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Phase-Peanut OIT | Incidence of All Serious Adverse Events During the Study | 0 number of discrete SAE events |
| Blinded Phase-Placebo | Incidence of All Serious Adverse Events During the Study | 0 number of discrete SAE events |
| Open Label Phase-Peanut OIT | Incidence of All Serious Adverse Events During the Study | 0 number of discrete SAE events |
Secondary
The Percentage of Subjects Achieving Full Desensitization as Defined by a Negative DBPCFC After 60 Months of Peanut OIT Therapy.
Upon completion of 60 months of peanut OIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCPFC) to assess desensitization. The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms after completing peanut OIT therapy.
Time frame: 60 months for those randomized to active treatment and 72 months for those randomized to placebo for the initial 12 months of therapy
Population: Subjects completing 60 months of OIT treatment and completing the DBPCFC on the last day of treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Phase-Peanut OIT | The Percentage of Subjects Achieving Full Desensitization as Defined by a Negative DBPCFC After 60 Months of Peanut OIT Therapy. | 100 percentage of participants |
Secondary
The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study
During the desensitization phase of the study, subjects under go an initial day escalation up to a maximum of 6 mg of peanut protein. They then undergo biweekly dose escalation over approximately 10 months up to a maximum dose of 4000 mg of peanut protein. This outcome reports the percentage of subjects that achieve this.
Time frame: approximately 40 weeks (10 months)
Population: Open label phase includes subjects initially randomized to placebo and then subsequently crossed over to open label treatment. Subjects initially randomized to Peanut OIT maintained their dose and did not re-escalate for the purposes of this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Phase-Peanut OIT | The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study | 90 percentage of patients |
| Blinded Phase-Placebo | The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study | 100 percentage of patients |
| Open Label Phase-Peanut OIT | The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study | 66.7 percentage of patients |
Secondary
The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut
The first day of peanut OIT dosing involved multiple increasing doses of peanut flour in what was called an initial escalation day up to a maximum dose of 6 mg of peanut protein. The secondary outcome measure assessed the percentage of subjects were successfully able to reach this 6 mg dose.
Time frame: first day of peanut OIT dosing
Population: Open label phase includes subjects initially randomized to placebo and then subsequently crossed over to open label treatment. Subjects initially randomized to Peanut OIT maintained their dose and did not repeat this 6 mg initial-day escalation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Phase-Peanut OIT | The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut | 90 percentage of participants |
| Blinded Phase-Placebo | The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut | 100 percentage of participants |
| Open Label Phase-Peanut OIT | The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut | 100 percentage of participants |