Cockroach Nasal Allergen Challenge Pilot

This is a multi-center, open label pilot study to assess the safety and determine the feasibility of cockroach nasal allergen challenge in children with asthma. This pilot study will occur in two phases:

• Phase 1 will enroll 10 cockroach sensitive adults with asthma who will undergo a nasal allergen challenge with increasing doses of cockroach allergen. Phase 1 will consist of two parts, Phase 1a and Phase 1b. In Phase 1a, participants will undergo a nasal allergen challenge. In Phase 1b, participants will undergo a repeat nasal allergen challenge to assess reproducibility of the NAC with cockroach allergen in a population with asthma. The data from Phase 1a will be used to identify a range of doses that is safe and elicits a threshold of nasal symptoms (TNSS ≥8).
• Phase 2 will enroll 25 cockroach sensitive children with asthma ages 8-14 years who will undergo a nasal allergen challenge using the dose range identified in Phase 1a.

Study mandated procedures include: blood draws (venipuncture); pulmonary function testing (PFTs); nasal allergen challenge (NAC); allergen skin testing; and peak expiratory flow.

Accrual Objective: N=10 adults, 25 children)

STUDY INCLUSION CRITERIA:

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

• Subject and/or parent guardian must be able to understand and provide informed consent.
• Male or female adults, 18 through 55 years of age at recruitment (Phase 1) or male or female children, 8-14 years of age at recruitment (Phase 2).
• Have a history of asthma for a minimum of 1 year before study entry:

• A diagnosis of asthma for this study is defined as a reported clinical diagnosis of asthma made by a physician over a year ago.
• The subject must have persistent asthma defined by the current need for at least 100 microgram (mcg) fluticasone per day or the equivalent of another inhaled corticosteroid.
• 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.
• Are sensitive to German Cockroach as documented by a positive (≥ 3 mm greater than negative control) skin prick test result and a positive German Cockroach specific immunoglobulin E (IgE) (≥0.35 kUA/L).
• Have no known contraindications to the allergenic extracts or diluents.
• Subjects who meet the following criteria are eligible for enrollment as study participants in Phase 1b after completion of Phase 1a:

• Their asthma must be well controlled as defined by:

• A FEV1 ≥ 80% predicted.
• An Asthma Control Test (ACT) score ≥ 20.
• The subject tolerated the Nasal Allergen Challenge (NAC) during Phase 1a with no adverse events grade 2 or higher as determined by "Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (published September 2007) for local reactions to study procedures."
• Subjects not eligible for enrollment as study participants in Phase 1b after completion of Phase 1a if any of the following criteria are met:

• Are pregnant or lactating.
• Have an asthma severity classification of severe persistent, using the NAEPP classification, as evidenced by at least one of the following:

• Require a dose of greater than 500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid.
• Have received more than 2 courses of oral or parenteral corticosteroids within the last 12 months or one course within the last 3 months.
• Have been treated with depot corticosteroids within the last 12 months.
• Have been hospitalized for asthma within the 12 months prior to their participation in Phase1b.
• Have had an emergency room visit for asthma within the 3 months prior to their participation in Phase 1b.
• Have had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to their participation in Phase 1b.
• Have received allergen immunotherapy (SLIT or SCIT) in the last 12 months prior to their participation in Phase 1b.
• Have previously been treated with anti-IgE therapy in the 12 months prior to their participation in Phase 1b.
• Are currently receiving oral or nasal antihistamines, nasal corticosteroids, nasal decongestants, nasal anticholinergics or cromolyn, which cannot be suspended for the required washout periods prior to the nasal allergen challenge in Phase 1b.
• Have received an investigational drug in the 30 days prior to their participation in Phase 1b.
• Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
• Meet any of the Participant Stopping Rules and Withdrawal Criteria during Phase 1a

• The participant elected to withdraw consent from all future study activities, including followup.
• The Investigator no longer believes participation is in the best interest of the 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 excessive discomfort or symptoms.
• Epistaxis occurring during the Challenge Visit.
• The need to start immunotherapy or any chronic immunosuppressive medications in the period between Phase 1a and Phase 1b.
• Require a dose of greater than 500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid to maintain asthma control in the period between Phase 1a and Phase 1b.
• Inability to restrict use of antihistamines, nasal steroids, nasal decongestants, 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"
• The subject's initial TNSS at the Repeat Challenge Visit must be within 1 point of the initial TNSS at the Challenge Visit in Phase 1a. If the participant's initial TNSS is outside the 1 point range, then the participant may be reevaluated 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 any portion of the study and may not be reassessed. Participants are ineligible if they:

• Plan to move from the area during the study period.
• Have a history of idiopathic anaphylaxis or anaphylaxis grade 2 or higher as defined by the grading scale of Brown et al. for anaphylaxis and systemic reactions to study procedures.
• Have unstable angina, significant arrhythmia, uncontrolled hypertension, history of autoimmune disease, or other chronic or immunological diseases that in the opinion of the investigator might interfere with the evaluation of the investigational agent or pose additional risk to the participant.
• Are using tricyclic antidepressants or beta-adrenergic blocker drugs (both oral and topical).

Exclusion criteria

SPECIFIC TO STUDY PHASE 1A AND -2:

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

• Are pregnant or lactating. Post-menarcheal females must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral, subcutaneous, mechanical, or surgical contraception).
• Cannot perform spirometry at Screening.
• Have an asthma severity classification at Recruitment of severe persistent, using the The National Asthma Education and Prevention Program (NAEPP) classification, as evidenced by at least one of the following:

• Require a dose of greater than 500mcg of fluticasone per day or the equivalent of another inhaled corticosteroid.
• Have received more than 2 courses of oral or parenteral corticosteroids within the last 12 months or one course within the last 3 months.
• Have been treated with depot corticosteroids within the last 12 months.
• Have been hospitalized for asthma within the 12 months prior to recruitment.
• Have had an emergency room visit for asthma within the 3 months prior to recruitment.
• Have had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to recruitment.
• Have nasal polyps or other major structural abnormalities in their nasal cavities as assessed by anterior rhinoscopy.
• Have active rhinitis symptoms prior to the nasal allergen challenge, defined as a Baseline Total Nasal Symptom Score(TNSS) >3,with no individual symptom score >1.
• Do not have access to a phone (needed for scheduling appointments).
• Have received allergen immunotherapy (Sublingual [SLIT] or Subcutaneous [SCIT]) in the last 12 months prior to recruitment or who plan to initiate or resume allergen immunotherapy during the study.
• Have previously been treated with anti-IgE therapy in the 12 months prior to recruitment.
• Are currently receiving oral or nasal antihistamines, nasal corticosteroids, nasal decongestants,nasal anticholinergics or cromolyn, which cannot be suspended for the required washout periods prior to skin prick testing and the nasal allergen challenge.
• Have received an investigational drug in the 30 days prior to recruitment or who plan to use an investigational drug during the study.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.