The Peanut Oral Immunotherapy Study: Safety, Efficacy and Discovery
Condition: Peanut Allergy
MeSH terms: Hypersensitivity; Peanut Hypersensitivity
Intervention: Peanut Protein 4,000mg; Oat Flour; Peanut Protein 300 mg
Intervention description: 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.; Arm C will be defined as "natural loss of responsiveness" if they show no clinical reactivity at DBPCFCs (week 117 to end of study).; 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).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 120.0
Sex: All
Minimum age: 7 Years
Maximum age: 55 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.