FARE Peanut SLIT and Early Tolerance Induction

Status:	Active, not recruiting
Conditions:	Allergy, Allergy, Allergy, Allergy, Allergy, Food Studies, Food Studies, Neurology
Therapuetic Areas:	Neurology, Otolaryngology, Pharmacology / Toxicology
Healthy:	No
Age Range:	Any
Updated:	10/14/2018
Start Date:	January 2015
End Date:	June 2020

Peanut Sublingual Immunotherapy Induction of Clinical Tolerance of Newly Diagnosed Peanut Allergic 12 to 48 Month Old Children

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). 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). 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, 39 months]

Secondary Objective: 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: 1) peanut specific IgE, IgG, and IgG4
response, 2) peanut specific basophil activation, 3) mast cell responses through skin prick
testing, and 4) specific T-cell cytokine responses and T regulatory cell (TReg) activation.
The investigators anticipate that the effect of peanut SLIT will occur by induction of TRegs,
conversion of T cells from an allergic (TH2) to a non-allergic (TH1) lymphocyte response
(measured by cytokines, antibody levels, and skin prick test size), a change in
peanut-specific basophil activation, or through a combination of the above.

[Time Frame: Baseline, 39 months]

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.

Inclusion Criteria:

- Written informed consent from participant's parent/guardian.

- Age 12-48 months of either sex, any race, any ethnicity.

- A peanut allergy diagnosis with a convincing clinical history of peanut allergy and a
serum peanut-specific IgE [UniCAP] > 0.35 kUA/L AND a positive skin prick test to
peanut (>3 mm than the negative control) OR are sensitized to peanut (based on a serum
IgE [UniCAP] to peanut of > 5 kUA/L) AND a positive skin prick test to peanut (> 3 mm
than the negative control) and no known history of ingestion of peanut.

- A positive DBPCFC to 1000 mg of peanut at enrollment.

Exclusion Criteria:

- History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or
neurologic compromise (cyanosis or SpO2 < 92% at any stage, hypotension, confusion,
collapse or loss of consciousness).

- Participation in any interventional study for the treatment of food allergy in the
past 6 months.

- Known oat, wheat, or glycerin allergy.

- Eosinophilic or other inflammatory (e.g. celiac) gastrointestinal disease.

- Severe asthma (2007 NHLBI Criteria Steps 5 or 6 - Appendix 2).

- Inability to discontinue antihistamines for skin testing and DBPCFCs.

- Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral
or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic
therapy within the past year.

- Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors,
angiotensin-receptor blockers (ARB) or calcium channel blockers.

- Significant medical condition (e.g., liver, kidney, gastrointestinal, cardiovascular,
hematologic, or pulmonary disease) which would make the subject unsuitable for
induction of food reactions.

We found this trial at

sites

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

(919) 962-2211