NCT02103270

The Peanut Oral Immunotherapy Study: Safety, Efficacy and Discovery

Single Center, Placebo Controlled Clinical Study in Desensitization vs Tolerance Induction in Peanut Allergy Subjects

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (actual)
• Sponsor: Stanford University · Academic / Other
• Sex: All
• Age: 7 Years – 55 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Peanut Allergy

Interventions

Type	Name	Description
DRUG	Peanut 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.
DRUG	Oat 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).
DRUG	Peanut 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).

Timeline

• Start date: 2014-04-01
• Primary completion: 2018-07-25
• Completion: 2018-09-01
• First posted: 2014-04-03
• Last updated: 2019-09-04
• Results posted: 2019-09-04

Locations

1 site across 1 country: United States