Sublingual Immunotherapy Studies for Grass and Dust Mite Allergies

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.