Peanut Hypersensitivity
Conditions
Keywords
Allergy, Peanut, Peanut allergy, Hypersensitivity, Immunotherapy, Desensitization, Immunologic
Brief summary
This is a randomized, double-blind, placebo-controlled, multi-center study comparing peanut oral immunotherapy (OIT) to placebo in the induction of tolerance and desensitization in peanut-allergic children. Eligible participants with peanut allergy will be randomly assigned to receive either peanut OIT or placebo for 134 weeks followed by peanut avoidance for 26 weeks.
Detailed description
An initial oral food challenge (OFC) to 1 g of peanut flour (500 mg peanut protein) will be conducted. Participants must have a clinical reaction during this OFC to initiate study dosing. After the initial OFC, the study design includes four phases: * Initial dose escalation (1 day): Peanut or placebo dosing will be given incrementally and increase every 20 minutes until a dose of 12 mg peanut flour (6 mg peanut protein) or placebo flour is given. * Build-up (30 weeks): Initial observed dose administration of highest tolerated dose, followed by daily OIT at home with return visit every 2 weeks for dose escalation. * Maintenance (104 weeks):The participant will continue on daily OIT with return visits every 13 weeks. At the end of this phase the participant will undergo a blinded OFC to 10 g peanut flour (5 g peanut protein). * Avoidance (26 weeks): In this final phase participants will be seen every 13 weeks. At the completion of this phase participants will have a final blinded OFC to 10g peanut flour (5 g peanut protein).
Interventions
BIOLOGICALPeanut Oral Immunotherapy - Liquid Extract
Used during initial dose escalation for doses 0.1 to 0.8 mg.
BIOLOGICALPlacebo for Peanut Oral Immunotherapy - Liquid Extract form
Similar in appearance, texture, and taste to peanut liquid extract.
BIOLOGICALPeanut Oral Immunotherapy - Peanut Flour
This will be used for the remainder of dose escalation, build-up, and maintenance.
BIOLOGICALPlacebo for Peanut Oral Immunotherapy - Peanut Flour
Similar in appearance, texture, and taste to peanut flour.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 48 Months
Healthy volunteers
No
Inclusion criteria
* Clinical history of peanut allergy or avoidance of peanut without ever having eaten peanut; * Serum immunoglobulin E (IgE) to peanut of ≥5 kUA/L determined by UniCAP™, an in-vitro test system for diagnosis and monitoring of allergy and inflammation; * Wheal ≥ 3mm on skin prick test to peanut extract compared to a negative control; * A clinical reaction at or below ingestion of 1 g peanut flour (500 mg peanut protein) during screening OFC; * Written informed consent from parent/guardian.
Exclusion criteria
* History of severe anaphylaxis with hypotension to peanut; * Documented clinical history of allergy to oat; * Suspected allergy to oat and a wheal ≥7mm on skin prick test to oat extract compared to a negative control; * Chronic disease other than asthma, atopic dermatitis, rhinitis requiring therapy; e.g., heart disease or diabetes; * Active eosinophilic gastrointestinal disease in the past 2 years; * Participation in any interventional study for the treatment of food allergy in the 6 months prior to visit -1; * Inhalant allergen immunotherapy that has not yet reached maintenance dosing; * Severe asthma, as indicated by repeated hospitalizations or hospital emergency department visits; * Moderate asthma defined according to National Asthma Education and Prevention Program Expert; * Panel that requires more than fluticasone 440 mcg or its equivalent daily for adequate control; * Inability to discontinue antihistamines for skin testing, OFC and the initial dose escalation; * Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) in the 12 months prior to visit -1; * Any systemic therapy which in the judgment of the investigator could be immunomodulatory (e.g. rituximab) in the 12 months prior to visit -1, systemic corticosteroid therapy of up to a total of three weeks is allowed; * Use of any investigational drug in 90 days prior to visit -1; * Plan to use any investigational drug during the study period; * The presence of any medical condition that the investigator deems incompatible with participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) | Week 134 | Definition of desensitized to peanut: A participant who passed the blinded (masked) oral food challenge (OFC) to10 grams of peanut flour (=5 grams of peanut protein) without significant symptoms.\* \*Significant symptoms include hives, wheezing, vomiting, or laryngeal edema. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Tolerant Participants at Week 160 | Week 160 | Definition of Tolerant: A participant who passed the oral food challenge (OFC) to 10 grams of peanut flour (=5 grams of peanut protein). |
| Count of Participants With Transient Desensitization | Week 134, Week 160 | Definition of transient desensitization: A participant who passed the blinded (masked) oral food challenge (OFC) to 10 grams peanut flour (=5 grams peanut protein) at week 134 and failed the week 160 in the Peanut oral immunotherapy (OIT) group. |
| Highest Tolerated Cumulative Dose | Week 160 | The highest tolerated cumulative dose of peanut protein during the blinded (masked) oral food challenge (OFC) at Week 160, analyzed within and between both placebo and peanut OIT groups. The highest cumulative dose of peanut protein tolerated for each participant was analyzed as a continuous outcome. Any randomized participant without an evaluable blinded (masked) OFC was imputed as not tolerant. For the continuous highest cumulative dose endpoint, this is defined as having a highest cumulative dose imputed as zero. |
| Percentage of Participants That Withdrew From the Study | Initial Dose Escalation through Week 160 (Tolerance Assessment) | Percentage of participants that withdrew from study participation, listed by study phase (at time of study withdrawal). |
Countries
United States
Participant flow
Recruitment details
Participants ages 1 to 3 with a clinical history of peanut allergy or avoidance of peanut without ever having eaten peanut were recruited from 5 clinical centers in the United States from August 2013 to October 2015.
Pre-assignment details
Individuals with a history of severe anaphylaxis (previous hypotension) to peanut were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Peanut Oral Immune Therapy (OIT) Peanut Oral Immune Therapy (OIT) for 134 weeks followed by peanut avoidance for 26 weeks.
Two forms of peanut oral immunotherapy were used. One form was a liquid extract derived from the peanut flour source material. This was used during initial dose escalation for doses 0.1 to 0.8 mg of peanut protein. The second form was peanut flour, which was used for the remainder of dose escalation, build-up, and maintenance. | 96 |
| Peanut Placebo Peanut placebo for 134 weeks followed by peanut avoidance for 26 weeks.
Two forms of placebo were used. One form was a liquid extract derived from oat flour source material. This was used during initial dose escalation for doses 0.1 to 0.8 mg. The second form was peanut flour, which was used for the remainder of dose escalation, build-up, and maintenance. | 50 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Anaphylaxis | 0 | 1 |
| Overall Study | Inability to reach 3 mg peanut/placebo | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance with Study Drug | 1 | 2 |
| Overall Study | Withdrawal by Subject | 21 | 21 |
Baseline characteristics
| Characteristic | Peanut Oral Immune Therapy (OIT) | Total | Peanut Placebo |
|---|---|---|---|
| Age, Continuous | 3.1 years STANDARD_DEVIATION 0.7 | 3.1 years STANDARD_DEVIATION 0.8 | 3.0 years STANDARD_DEVIATION 0.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants | 137 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 18 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 16 Participants | 27 Participants | 11 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 | 64 Participants | 95 Participants | 31 Participants |
| Region of Enrollment United States | 96 participants | 146 participants | 50 participants |
| Sex: Female, Male Female | 30 Participants | 48 Participants | 18 Participants |
| Sex: Female, Male Male | 66 Participants | 98 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 50 |
| other Total, other adverse events | 96 / 96 | 50 / 50 |
| serious Total, serious adverse events | 3 / 96 | 4 / 50 |
Outcome results
Primary
Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT)
Definition of desensitized to peanut: A participant who passed the blinded (masked) oral food challenge (OFC) to10 grams of peanut flour (=5 grams of peanut protein) without significant symptoms.\* \*Significant symptoms include hives, wheezing, vomiting, or laryngeal edema.
Time frame: Week 134
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) | 71 Percentage of Participants |
| Peanut Placebo | Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) | 2 Percentage of Participants |
p-value: <0.000195% CI: [24, 1758.51]Regression, Logistic
Secondary
Count of Participants With Transient Desensitization
Definition of transient desensitization: A participant who passed the blinded (masked) oral food challenge (OFC) to 10 grams peanut flour (=5 grams peanut protein) at week 134 and failed the week 160 in the Peanut oral immunotherapy (OIT) group.
Time frame: Week 134, Week 160
Population: Participants randomized to the Peanut Oral Immunotherapy (OIT) group
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peanut Oral Immune Therapy (OIT) | Count of Participants With Transient Desensitization | Passed Week 134 and Failed Week 160 | 49 Participants |
| Peanut Oral Immune Therapy (OIT) | Count of Participants With Transient Desensitization | Passed Week 134 and Passed Week 160 | 19 Participants |
| Peanut Oral Immune Therapy (OIT) | Count of Participants With Transient Desensitization | Failed Week 134 and Failed Week 160 | 27 Participants |
| Peanut Oral Immune Therapy (OIT) | Count of Participants With Transient Desensitization | Failed Week 134 and Passed Week 160 | 1 Participants |
p-value: <0.000195% CI: [0.0628, 0.2612]McNemar
Secondary
Highest Tolerated Cumulative Dose
The highest tolerated cumulative dose of peanut protein during the blinded (masked) oral food challenge (OFC) at Week 160, analyzed within and between both placebo and peanut OIT groups. The highest cumulative dose of peanut protein tolerated for each participant was analyzed as a continuous outcome. Any randomized participant without an evaluable blinded (masked) OFC was imputed as not tolerant. For the continuous highest cumulative dose endpoint, this is defined as having a highest cumulative dose imputed as zero.
Time frame: Week 160
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Peanut Oral Immune Therapy (OIT) | Highest Tolerated Cumulative Dose | 1645 mg protein |
| Peanut Placebo | Highest Tolerated Cumulative Dose | 180 mg protein |
p-value: <0.000195% CI: [944, 1985]Chi-squared
Secondary
Percentage of Participants That Withdrew From the Study
Percentage of participants that withdrew from study participation, listed by study phase (at time of study withdrawal).
Time frame: Initial Dose Escalation through Week 160 (Tolerance Assessment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated during Maintenance | 8 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated during Avoidance | 11 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated during Build-Up | 4 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated after Avoidance/Prior to OFC | 0 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated after Maintenance/Prior to OFC | 1 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated after Tolerance Assessment | 3 percentage of participants |
| Peanut Oral Immune Therapy (OIT) | Percentage of Participants That Withdrew From the Study | Terminated during Initial Dose Escalation | 2 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated after Tolerance Assessment | 2 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated during Initial Dose Escalation | 0 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated during Build-Up | 12 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated during Maintenance | 16 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated after Maintenance/Prior to OFC | 2 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated during Avoidance | 14 percentage of participants |
| Peanut Placebo | Percentage of Participants That Withdrew From the Study | Terminated after Avoidance/Prior to OFC | 10 percentage of participants |
Secondary
Percentage of Tolerant Participants at Week 160
Definition of Tolerant: A participant who passed the oral food challenge (OFC) to 10 grams of peanut flour (=5 grams of peanut protein).
Time frame: Week 160
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peanut Oral Immune Therapy (OIT) | Percentage of Tolerant Participants at Week 160 | 21 percentage of participants |
| Peanut Placebo | Percentage of Tolerant Participants at Week 160 | 2 percentage of participants |
p-value: <0.003195% CI: [3.07, 252.33]Regression, Logistic