Cockroach Nasal Allergen Challenge Pilot

Accrual Objective: N=10 adults, 25 children) STUDY INCLUSION CRITERIA:

• Subjects fulfilling all of the following criteria are eligible for enrollment as studyparticipants for Phase 1a and Phase 2:

1. Subject and/or parent guardian must be able to understand and provide informedconsent.

2. Male or female adults, 18 through 55 years of age at recruitment (Phase 1) ormale or female children, 8‐14 years of age at recruitment (Phase 2).

3. Have a history of asthma for a minimum of 1 year before study entry:

4. A diagnosis of asthma for this study is defined as a reported clinicaldiagnosis of asthma made by a physician over a year ago.

5. The subject must have persistent asthma defined by the current need for atleast 100 microgram (mcg) fluticasone per day or the equivalent of anotherinhaled corticosteroid.

6. The subject's asthma must be well controlled as defined by:

• A Forced Expiratory Volume in 1 Second (FEV1) ≥ 80% predicted.

• An Asthma Control Test (ACT) score ≥ 20.

4. Are sensitive to German Cockroach as documented by a positive (≥ 3 mm greaterthan negative control) skin prick test result and a positive German Cockroachspecific immunoglobulin E (IgE) (≥0.35 kUA/L).

5. Have no known contraindications to the allergenic extracts or diluents.

• Subjects who meet the following criteria are eligible for enrollment as studyparticipants in Phase 1b after completion of Phase 1a:

1. Their asthma must be well controlled as defined by:

2. A FEV1 ≥ 80% predicted.

3. An Asthma Control Test (ACT) score ≥ 20.

4. The subject tolerated the Nasal Allergen Challenge (NAC) during Phase 1a with noadverse events grade 2 or higher as determined by "Guidance for Industry:Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled inPreventive Vaccine Clinical Trials (published September 2007) for local reactionsto study procedures."

• Subjects not eligible for enrollment as study participants in Phase 1b aftercompletion of Phase 1a if any of the following criteria are met:

1. Are pregnant or lactating.

2. Have an asthma severity classification of severe persistent, using the NAEPPclassification, as evidenced by at least one of the following:

3. Require a dose of greater than 500 mcg of fluticasone per day or theequivalent of another inhaled corticosteroid.

4. Have received more than 2 courses of oral or parenteral corticosteroidswithin the last 12 months or one course within the last 3 months.

5. Have been treated with depot corticosteroids within the last 12 months.

6. Have been hospitalized for asthma within the 12 months prior to theirparticipation in Phase1b.

7. Have had an emergency room visit for asthma within the 3 months prior totheir participation in Phase 1b.

8. Have had a life‐threatening asthma exacerbation that required intubation,mechanical ventilation, or that resulted in a hypoxic seizure within 2 yearsprior to their participation in Phase 1b.

9. Have received allergen immunotherapy (SLIT or SCIT) in the last 12 months priorto their participation in Phase 1b.

10. Have previously been treated with anti‐IgE therapy in the 12 months prior totheir participation in Phase 1b.

11. Are currently receiving oral or nasal antihistamines, nasal corticosteroids,nasal decongestants, nasal anticholinergics or cromolyn, which cannot besuspended for the required washout periods prior to the nasal allergen challengein Phase 1b.

12. Have received an investigational drug in the 30 days prior to their participationin Phase 1b.

13. Have past or current medical problems or findings from physical examination orlaboratory testing that are not listed above, which, in the opinion of theinvestigator, may pose additional risks from participation in the study, mayinterfere with the subject's ability to comply with study requirements or thatmay impact the quality or interpretation of the data obtained from the study.

14. Meet any of the Participant Stopping Rules and Withdrawal Criteria during Phase 1a

• The participant elected to withdraw consent from all future studyactivities, including followup.

• The Investigator no longer believes participation is in the best interest ofthe participant.

• Serious Adverse Event (SAE) related to investigational product.

• Anaphylactic reaction grade 2 or 3.

• Inability to tolerate the NAC prior to reaching a TNSS ≥8 due to excessivediscomfort or symptoms.

• Epistaxis occurring during the Challenge Visit.

• The need to start immunotherapy or any chronic immunosuppressive medicationsin the period between Phase 1a and Phase 1b.

• Require a dose of greater than 500 mcg of fluticasone per day or theequivalent of another inhaled corticosteroid to maintain asthma control inthe period between Phase 1a and Phase 1b.

• Inability to restrict use of antihistamines, nasal steroids, nasaldecongestants, nasal anticholinergics or cromolyn prior to the NAC.

• Development of any serious medical illness whose natural history, sequela,or treatment would be worsened or impaired by continuation in the protocol.

• Subject is "lost to follow‐up"

9. The subject's initial TNSS at the Repeat Challenge Visit must be within 1 pointof the initial TNSS at the Challenge Visit in Phase 1a. If the participant'sinitial TNSS is outside the 1 point range, then the participant may bereevaluated for the Repeat Challenge Visit up to 3 additional times.

STUDY EXCLUSION CRITERIA: Subjects fulfilling any of the following criteria are not eligible for enrollment in anyportion of the study and may not be reassessed. Participants are ineligible if they:

1. Plan to move from the area during the study period.

2. Have a history of idiopathic anaphylaxis or anaphylaxis grade 2 or higher as definedby the grading scale of Brown et al. for anaphylaxis and systemic reactions to studyprocedures.

3. Have unstable angina, significant arrhythmia, uncontrolled hypertension, history ofautoimmune disease, or other chronic or immunological diseases that in the opinion ofthe investigator might interfere with the evaluation of the investigational agent orpose additional risk to the participant.

4. Are using tricyclic antidepressants or beta‐adrenergic blocker drugs (both oral andtopical). EXCLUSION CRITERIA SPECIFIC TO STUDY PHASE 1A AND -2:

• Subjects who meet any of these criteria are not eligible for enrollment as studyparticipants in Phase1a and Phase 2:

1. Are pregnant or lactating. Post‐menarcheal females must be abstinent or use amedically acceptable birth control method throughout the study (e.g. oral,subcutaneous, mechanical, or surgical contraception).

2. Cannot perform spirometry at Screening.

3. Have an asthma severity classification at Recruitment of severe persistent, usingthe The National Asthma Education and Prevention Program (NAEPP) classification,as evidenced by at least one of the following:

4. Require a dose of greater than 500mcg of fluticasone per day or theequivalent of another inhaled corticosteroid.

5. Have received more than 2 courses of oral or parenteral corticosteroidswithin the last 12 months or one course within the last 3 months.

6. Have been treated with depot corticosteroids within the last 12 months.

7. Have been hospitalized for asthma within the 12 months prior to recruitment.

8. Have had an emergency room visit for asthma within the 3 months prior torecruitment.

9. Have had a life‐threatening asthma exacerbation that required intubation,mechanical ventilation, or that resulted in a hypoxic seizure within 2 yearsprior to recruitment.

10. Have nasal polyps or other major structural abnormalities in their nasal cavitiesas assessed by anterior rhinoscopy.

11. Have active rhinitis symptoms prior to the nasal allergen challenge, defined as aBaseline Total Nasal Symptom Score(TNSS) >3,with no individual symptom score >1.

12. Do not have access to a phone (needed for scheduling appointments).

13. Have received allergen immunotherapy (Sublingual [SLIT] or Subcutaneous [SCIT])in the last 12 months prior to recruitment or who plan to initiate or resumeallergen immunotherapy during the study.

14. Have previously been treated with anti‐IgE therapy in the 12 months prior torecruitment.

15. Are currently receiving oral or nasal antihistamines, nasal corticosteroids,nasal decongestants,nasal anticholinergics or cromolyn, which cannot be suspendedfor the required washout periods prior to skin prick testing and the nasalallergen challenge.

16. Have received an investigational drug in the 30 days prior to recruitment or whoplan to use an investigational drug during the study.

17. Past or current medical problems or findings from physical examination orlaboratory testing that are not listed above, which, in the opinion of theinvestigator, may pose additional risks from participation in the study, mayinterfere with the participant's ability to comply with study requirements orthat may impact the quality or interpretation of the data obtained from thestudy.