Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance

Allergy to peanuts and tree nuts affects approximately 1.4% of the population. Allergic
reactions to peanut can be severe and life threatening and account for the vast majority of
fatalities due to food-induced anaphylaxis. At present, there are no viable treatment options
for patients with peanut allergy. The current standard of care is strict dietary elimination
and emergency preparedness with an anaphylaxis kit in the event of an accidental reaction.

Our group and others have shown that oral immunotherapy can provide protection from
anaphylaxis to a variety of food proteins. In addition, our ongoing research has demonstrated
that sublingual immunotherapy to peanut provides a safe, alternative mode of immunotherapy to
reduce allergic reaction rates (desensitization) during oral food challenge (OFC) to peanut.
The goal of this study will be to desensitize peanut allergic children using peanut
sublingual immunotherapy and to determine if the nonreactive state of the immune system
persists after treatment has been discontinued (tolerance). Children ages 1-11 years will be
enrolled following an entry double blind, placebo controlled food challenge (DBPCFC).

After at least 48 months of peanut SLIT study drug, subjects will undergo a second DBPCFC to
5000 mg of peanut protein to assess desensitization.

- Subjects who are not desensitized are those who are not able to consume more than the
MCRT without symptoms, which has been defined as 300 mg of peanut protein. Subjects who
consume less than 300 mg of peanut protein without symptoms will stop peanut SLIT and
conclude the study. These subjects will not undergo any additional study procedures
including the remaining protocol DBPCFCs and will be recommended to resume a strict
peanut avoidance diet.

- Subjects who are able to consume more than 300 mg of peanut protein will be randomized
to an interval between 1 and 17 weeks during which all peanut including peanut SLIT
study drug will be discontinued. This period of avoidance will be followed by a third
DBPCFC to 5000 mg of peanut protein to evaluate for the loss of the desensitization
effect. After this final DBPCFC, the study will be completed for these subjects. At the
primary investigators clinical discretion, they will be recommended to transition to a
daily peanut food equivalent to maintain the desensitized effect.

Outcome variables of interest include response to double blind, placebo controlled food
challenges, skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G
(IgG), and immunoglobin G4 (IgG4) and salivary immunoglobin A (IgA), T and B cell responses,
basophil hyporesponsiveness, quality of life, and adverse events.

Inclusion Criteria:

- Age 1-11 years

- Peanut specific IgE > 0.35kU/L or a convincing clinical history of an allergic
reaction to peanut within 1 hour of ingestion

- Positive entry DBPCFC to 1 gram of peanut protein

Exclusion Criteria:

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

- 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 National Heart Lung and Blood Institute (NHLBI) guidelines
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