Peanut Allergy
Conditions
Brief summary
Determine whether peanut oral immunotherapy (OIT) induces clinical tolerance as assessed after the initial 3 month avoidance period Secondary Objectives: * Identify the basic immune mechanisms which can explain the differences in the effects of OIT in desensitized vs. tolerant individuals. * Determine whether immune monitoring measurements reflecting underlying mechanisms during OIT can be used to predict responses to OIT in individual subjects and, ultimately, to improve the safety and efficacy outcomes in peanut OIT protocols.
Detailed description
All arms will undergo an Initial Dose Escalation (IDE) Day and updosing regimen with a maintenance phase of OIT or placebo to a maximum of 4,000 mg protein daily, as peanut flour, in the OIT groups, and to a maximum of an equivalent amount of oat flour for the placebo group. After maintenance is achieved, all subjects will begin performing DBPCFCs (staged so as to ensure safety) at Week 104 and every 13 weeks thereafter. At Week 104, individuals that reach criteria will, based on the randomization that was done at the start of the study, either stop therapy with peanut and be switched to oat flour, or will be maintained on 300 mg peanut protein per day and all placebo subjects will decrease to the equivalent volume of oat flour (approximately 600 mg oat flour) to optimize the blind. All subjects will be evaluated every 13 weeks thereafter with DBPCFCs until the end of study. Individuals in Arm A will be defined as clinically tolerant if there is no clinical reactivity at the Week 104 and Week 117 DBPCFC. Clinical reactivity is defined as any reaction ≥ Grade 1 based on the Bock's Criteria. Individuals in Arm A who meet the definition of clinically tolerant will continue to avoid peanut protein (i.e. continue on 600 mg per day of oat flour) as long as each subsequent DBPCFC (performed every 13 weeks until end of study) shows no clinical reactivity. Individuals in Arm B will be defined as desensitized to a minimum of 300 mg per day of peanut protein if they show no clinical reactivity at DBPCFCs (week 117 to end of study). Individuals in Arm C will be defined as natural loss of responsiveness if they show no clinical reactivity at DBPCFCs (week 117 to end of study). We plan to identify the basic immune mechanisms which can explain the differences in the effects of OIT in individuals who do or do not become clinically tolerant and to determine whether immune monitoring can predict the safety and efficacy outcomes in peanut OIT protocols. After initial screening and enrollment, there are three phases of the study: * Dose escalation and Build up Phase * Maintenance phase * Tolerance and Desensitization Testing phase Overall, 120 subjects who are eligible will undergo the Initial Dose Escalation Day. Subsequent updosing visits will occur every 2 weeks as a part of the build-up phase. They will continue to updose until they reach 4,000 mg protein daily, which is the maximum maintenance amount of protein. We expect active OIT treatment subjects to reach 4,000 mg of peanut protein between 44-78 weeks. Treatment and Desensitization Failures: A treatment failure will be defined as a) failure to reach 1.5 mg peanut protein (single dose) during the Initial Dose Escalation Day or b) failure to reach 1,000 mg peanut protein by week 104. Subjects who do not meet the criteria at Week 104 and who demonstrate clinical reactivity will be considered desensitization failures. If Arm B subjects demonstrate clinical reactivity in any DBPCFC from Week 117 to end of study, they will be considered desensitization failures. If Arm A subjects demonstrate clinical reactivity (≥Grade 1, in any DBPCFC from Week 117 to end of study, they will be considered tolerance failures. Treatment failures, desensitization failures, and tolerance failures will be unblinded (both participant and research staff) and will be followed until the end of the study at the specified study visits but will not undergo DBPCFCs. They will be considered in statistical analyses of the intent-to-treat population.
Interventions
DRUGPeanut Protein 4,000mg
Arm A will be defined as clinically tolerant if there is no clinical reactivity at the Week 104 and Week 117 DBPCFC. Clinical reactivity is defined as any reaction ≥ Grade 1 based on the Bock's Criteria (Appendix 4). Individuals in Arm A who meet the definition of clinically tolerant will continue to avoid peanut protein (i.e. continue on 600 mg per day of oat flour) as long as each subsequent DBPCFC (performed every 13 weeks until end of study) shows no clinical reactivity.
DRUGOat Flour
Arm C will be defined as natural loss of responsiveness if they show no clinical reactivity at DBPCFCs (week 117 to end of study).
DRUGPeanut Protein 300 mg
Arm B will be defined as desensitized to a minimum of 300 mg per day of peanut protein if they show no clinical reactivity at DBPCFCs (week 117 to end of study).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Subject and/or parent guardian must be able to understand and provide informed consent and/or assent as applicable. * Peanut-allergic subjects between the ages of 7-55 years old. * Sensitivity to peanut allergen as documented by a positive skin prick test result (5 mm or greater diameter wheal relative to negative control) within 10 months preceding enrollment. * Allergy to peanut based on a double-blind placebo-controlled oral food challenge (DBPCFC) (see Appendix 4 for scoring details) failed at a dose ≤500 mg with peanut protein within 10 months preceding enrollment. * All female subjects of child-bearing potential will be required to provide a blood or urine sample for pregnancy testing that must be negative one week before being allowed to participate in the study. * Subjects must plan to remain in the study area during the trial. * Subjects must be trained on the proper use of the EpiPen (see Appendix 6) to be allowed to enroll in the study. * Subjects with other food allergies must agree to eliminate these other food items from their diet so as not to confound the safety and efficacy data from the study. * Use of birth control by female subjects of child-bearing potential
Exclusion criteria
* Inability or unwillingness of a participant to give written informed consent or comply with study protocol * History of cardiovascular disease * History of other chronic disease (other than asthma, atopic dermatitis, or rhinitis) requiring therapy (e.g., heart disease, diabetes) that, in the opinion of the Principal Investigator, would represent a risk to the subject's health or safety in this study or the subject's ability to comply with the study protocol * History of eosinophilic gastrointestinal disease * Current participation in any other interventional study * Subject is on 'build-up phase of immunotherapy to another allergen (i.e., has not reached maintenance dosing) * Severe asthma (2007 NHLBI Criteria Steps 5 or 6) at time of enrollment * • Use of complementary and alternative medicine (CAM) treatment modalities (e.g., herbal remedies) for atopic and/or non-atopic disease within 90 days preceding Initial Dose Escalation Day (IDED) or at any time after the IDED * Inability to discontinue antihistamines for the initial day of escalation, skin testing or OFCs * Use of omalizumab within the past six months, or current use of other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) * Use of β-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers * Pregnancy or lactation * History of sensitivity to oat * History of severe anaphylaxis to peanut with symptoms including hypotension requiring fluid resuscitation and/or the need for mechanical ventilation * Use of investigational drugs within 24 weeks of participation * Past or current medical problems or findings from physical assessment or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Passing the Week 117 DBPCFC to Peanut | Week 117 - Number of participants with no clinical reactivity to peanuts | Number of Participants with No Clinical Reactivity to Peanuts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Passing the DBPCFC to Peanut at Week 130 | Week 130 | Secondary endpoint: Passing the DBPCFC to peanut at 130 weeks |
Countries
United States
Participant flow
Recruitment details
All arms undergo an Initial Dose Escalation (IDE) Day and updosing regimen with a maintenance phase of OIT or placebo to a maximum of 4,000 mg protein daily, as peanut flour, in the OIT groups, and to a maximum of an equivalent amount of oat flour for the placebo group.
Pre-assignment details
At Week 104, individuals that reach criteria will, based on the randomization, either stop therapy with peanut and be switched to oat flour or will maintain on 300 mg peanut protein per day and all placebo subjects decreased to the equivalent volume of oat flour to optimize the blind. All subjects were evaluated every 13 weeks with DBPCFCs.
Participants by arm
| Arm | Count |
|---|---|
| Peanut 4000 Oral immunotherapy with peanut discontinuation arm | 60 |
| Peanut 300 Oral immunotherapy with low dose peanut continuation arm. | 35 |
| Placebo Comparator: Oat Flour 600 mg Placebo received oat flour | 25 |
| Total | 120 |
Baseline characteristics
| Characteristic | Placebo Comparator: Oat Flour 600 mg | Total | Peanut 4000 | Peanut 300 |
|---|---|---|---|---|
| Age, Continuous | 11 years | 11 years | 10 years | 11 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 11 Participants | 9 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 109 Participants | 51 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 25 participants | 120 participants | 60 participants | 35 participants |
| Sex: Female, Male Female | 6 Participants | 39 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Male | 19 Participants | 81 Participants | 39 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 35 | 0 / 25 |
| other Total, other adverse events | 0 / 60 | 0 / 35 | 0 / 25 |
| serious Total, serious adverse events | 1 / 60 | 1 / 35 | 0 / 25 |
Outcome results
Primary
Passing the Week 117 DBPCFC to Peanut
Number of Participants with No Clinical Reactivity to Peanuts
Time frame: Week 117 - Number of participants with no clinical reactivity to peanuts
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peanut 4000 | Passing the Week 117 DBPCFC to Peanut | 21 participants |
| Peanut 300 | Passing the Week 117 DBPCFC to Peanut | 19 participants |
| Placebo Comparator: Oat Flour 600 mg | Passing the Week 117 DBPCFC to Peanut | 1 participants |
Secondary
Passing the DBPCFC to Peanut at Week 130
Secondary endpoint: Passing the DBPCFC to peanut at 130 weeks
Time frame: Week 130
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peanut 4000 | Passing the DBPCFC to Peanut at Week 130 | 12 participants |
| Peanut 300 | Passing the DBPCFC to Peanut at Week 130 | 15 participants |
| Placebo Comparator: Oat Flour 600 mg | Passing the DBPCFC to Peanut at Week 130 | 1 participants |