Sublingual Immunotherapy Studies for Grass and Dust Mite Allergies

This is a phase I, single-center, randomized, placebo-controlled study of sublingual
immunotherapy (SLIT) in pediatric and adult subjects with both house dust mite (HDM) and
timothy grass (TG) allergies. We will evaluate whether Dermatophagoides farinae (DF) and/or
TG allergen SLIT is safe in children and adults. We will also determine whether treatment
with DF and/or TG SLIT reduces the severity of allergic symptoms (allergic rhinitis,
allergic conjunctivitis) and enhances their resolution. The study will also evaluate whether
SLIT provides a robust durability of response once it is terminated. The dosing-phase of the
study will last up to 12 months. In addition, a follow up period of 2 years will occur.
Approximately 10 subjects will be on placebo, and 20 on active treatment.

SUBJECT INCLUSION CRITERIA:

1. Pediatric and adult timothy grass- and Dermatophagoides farinae-sensitive subjects
with allergic rhinoconjunctivitis with or without asthma perennially or during grass
pollen season.

2. Subjects must be 5 years of age or older.

3. Sensitivity to the relevant allergen will be documented by a positive skin prick test
result (see Appendix E for details).

4. All female subjects of child-bearing potential will be required to provide a urine
sample for pregnancy testing that must be negative one week before being allowed to
participate in the study.

5. Subjects must be planning to remain in the study area during the trial.

6. Subjects and/or their parents must be trained on the proper use of the Epi-Pen to be
allowed to enroll in the study.

7. Subjects and/or their parents must be mentally and physically capable of
self-administering oral drug.

SUBJECT EXCLUSION CRITERIA:

No absolute contraindications to allergen skin testing and/or sublingual immunotherapy are
known. However, the risk of serious systemic anaphylactic reactions to pollen or any
potent allergenic extract suggests a number of preexisting conditions that should be
considered relative contraindications. Among those conditions are acute infections,
autoimmune disease, severe cardiac disease, and treatment with beta-adrenergic
antagonistic drugs (beta-blockers).

1. Subjects having a history of unexplained anaphylaxis within 2 years or a history of
multiple (≥2) episodes of anaphylaxis in the past year, frequent allergic or
non-allergic urticaria, or history consistent with poorly controlled persistent
asthma. Anaphylaxis must be medically diagnosed.

2. Subjects with unstable angina, significant arrhythmia, uncontrolled hypertension,
chronic sinusitis, or other chronic or immunological diseases that in the mind of the
investigator might interfere with the evaluation or administration of the test drug
or pose additional risk to the subject e.g. gastrointestinal or gastroesophageal
disease, chronic infections, scleroderma, hepatic and gallbladder disease, chronic
non-allergic pulmonary disease.

3. Subject with an FEV1 or PEF less than 80% predicted (moderate persistent asthma) with
or without controller medication.

4. Subjects who have received an experimental drug in the last 30 days prior to
admission into this study or who plan to use an experimental drug during the study.

5. Subjects who have received timothy grass or dust mite allergen immunotherapy within 3
years prior to admission in this study.

6. Subjects who are current users of oral, intramuscular, or intravenous
corticosteroids, tricyclic antidepressants, or are taking a beta-blocker (oral or
topical).

7. Subjects routinely using medication that could induce adverse gastrointestinal
reactions during the study.

8. Subjects refusing to sign the EpiPen Training Form (see Appendix F).

9. Pregnant or breast feeding females.

10. Subjects who have any symptoms at dose levels 1 or 2 at the Preliminary Dosing Visit
(see, below).

11. Subjects with significant pet allergies who have significant exposure at home or at
work.