FARE Peanut SLIT and Early Tolerance Induction
Condition: Peanut Hypersensitivity; Food Allergy; Food Hypersensitivity; Peanut Allergy
MeSH terms: Hypersensitivity; Food Hypersensitivity; Peanut Hypersensitivity
Study type: Interventional
Phase: Phase 2

Summary: 
      Primary Objective: To determine if 36 months of peanut SLIT as an early intervention in
      subjects ages 1 to 4 years induces clinical desensitization. The primary outcome of this
      objective will be a statistically significant difference in challenge scores between the
      treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food
      challenge) performed after 36 months of peanut SLIT (desensitization). Challenge scores are
      measured by the amount of peanut protein participants are able to ingest successfully without
      symptoms of an allergic reaction. [Time Frame: Baseline, 36 months]

      Secondary Objectives:

      A secondary outcome of this objective will be a statistically significant difference in the
      challenge score of the treatment group versus the placebo group during the DBPCFC performed 3
      months after discontinuing therapy (tolerance).

      To examine the change in immune parameters associated with peanut SLIT and the development of
      clinical tolerance. Through this objective, the investigators will seek to understand the
      molecular processes by which SLIT affects the immune system through evaluation of immune
      mechanisms in relationship to clinical findings of desensitization and tolerance. The
      investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral
      responses to peanut protein.

      [Time Frame: Baseline, 39 months]
    

Detailed description: 
      Peanut allergy is one of the most common food allergies; most children develop this allergy
      early in life, do not outgrow it and are at risk for severe and life-ending anaphylactic
      reactions. There is a critical need for a proactive treatment for peanut allergy and the
      investigators along with others are developing specific types of immunotherapy that will act
      as disease-modifying therapies.

      This SLIT study is a randomized, blinded, placebo-controlled study. The primary outcome of
      this objective will be a statistically significant difference in challenge scores between the
      treatment group versus the placebo group during DBPCFC performed after 36 months of peanut
      SLIT (desensitization). A secondary outcome of this objective will be a statistically
      significant difference in the challenge score of the treatment group versus the placebo group
      during the DBPCFC performed 3 months after discontinuing therapy (tolerance).

      Upon enrollment into the study, all subjects will undergo a qualifying entry DBPCFC with
      peanut protein to confirm the diagnosis of peanut allergy and establish a baseline threshold
      level. Following a positive DBPCFC, each subject will be randomized 1:1 to receive peanut
      SLIT therapy versus placebo for a duration of 36 months. DBPCFC will be repeated for both
      active and placebo subjects at 36 months to assess desensitization and at 39 months to assess
      tolerance.

      Outcome variables of interest include peanut specific IgE, IgG, and IgG4, basophil
      activation, mast cell responses through skin prick testing, and specific T-cell cytokine
      responses and T regulatory cell (TReg) activation.

      COVID-19 SAFETY MEASURES- Reflected in Protocol V4.0- April 2020

      In March of 2020, State and National emergencies were declared over the global pandemic
      coronavirus COVID-19.

      As such, any 36 month Desensitization DBPCFC will be postponed while the safety measures
      surrounding COVID-19 are in place. Subjects who choose to remain in the study will continue
      on study drug at the maintenance dose level beyond the originally planned 36 months until
      such time that the Desensitization DBPCFC is conducted.

      Subjects who are scheduled to undergo the 39 month Tolerance DBPCFC while the COVID-19 safety
      measures are in place will have their DBPCFC cancelled. Additional time off of study drug
      therapy would potentially increase the risk of allergic reaction during the DBPCFC and would
      not be acceptable.

      For subjects whose Desensitization DBPCFC is postponed, a followup visit to review safety and
      subject dosing diaries would be conducted. This visit would be conducted remotely by
      telephone. Additional study drug would be sent direct-to-patient as necessary to continue on
      maintenance dosing. Lab sample collection and mechanistic studies would be deferred and be
      completed at the time that the Desensitization DBPCFC is completed. The Tolerance DBPCFC
      would be completed 3 months after the Desensitization DBPCFC is completed.

      For subjects whose Tolerance DBPCFC is canceled, an exit visit would be conducted to review
      safety. The subject would be unblinded to treatment allocation and end of study instructions
      would be reviewed with the subject.

      As the situation is changing daily, we are unable to provide a time frame for extension. We
      hope to limit the number of subjects who will need to utilize this option and preserve the
      endpoint data parameters. Previous SLIT studies have not shown any additional risk with
      peanut SLIT dosing beyond 3 years up to a total of 5 years of dosing.
    

Intervention name(s): Liquid Peanut Extract; Placebo Glycerin SLIT
Intervention type(s): Drug; Drug
Intervention description(s): 5000mcg/ml peanut protein; pure glycerinated saline solution with caramel coloring to match color
Other intervention name(s): SLIT; SLIT
Intervention MeSH terms: Glycerol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Peanut; Food Allergy