The Peanut Oral Immunotherapy Study: Safety, Efficacy and Discovery
Condition: Peanut Allergy
MeSH terms: Hypersensitivity; Peanut Hypersensitivity
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Peanut Protein 4,000mg; Oat Flour; Peanut Protein 300 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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).
Other intervention name(s): Peanut Flour; Peanut Flour
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment