Cockroach Nasal Allergen Challenge Pilot
Condition: Asthma; Cockroach Hypersensitivity
MeSH terms: Asthma; Hypersensitivity
Intervention: Glycerinated German Cockroach Allergenic Extract
Intervention description: Participants will receive escalating doses intranasally. Briefly: per protocol- Phase 1a NAC: N=10 cockroach sensitive adults with asthma will undergo nasal allergen challenge with dose escalation (up to 8 doses per protocol). Phase 1b: Phase 1a subjects will have repeat NAC with dose escalation (up to 8 doses).
Phase 2: N=25 cockroach sensitive children with asthma (ages 8 - 14 years) will undergo NAC with doses determined by Phase 1a data (e.g., symptoms and safety data).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 8 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Asthma; Glycerinated German cockroach allergenic extract; Cockroach Nasal Allergen Challenge

Summary:

      This research is being done to look at the body's response to cockroach extract, an allergen,
      when sprayed into the nose. The spraying of the cockroach extract into the participant's nose
      is called Nasal Allergen Challenge (NAC). The purpose of this study is to evaluate the safety
      and tolerability of a intranasal cockroach extract given to participants with asthma.
    

Eligibility criteria:

        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:

               1. Subject and/or parent guardian must be able to understand and provide informed
                  consent.

               2. 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).

               3. Have a history of asthma for a minimum of 1 year before study entry:

                    1. A diagnosis of asthma for this study is defined as a reported clinical
                       diagnosis of asthma made by a physician over a year ago.

                    2. 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.

                    3. 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 greater
                  than negative control) skin prick test result and a positive German Cockroach
                  specific 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 study
             participants in Phase 1b after completion of Phase 1a:

               1. Their asthma must be well controlled as defined by:

                    1. A FEV1 ≥ 80% predicted.

                    2. An Asthma Control Test (ACT) score ≥ 20.

               2. 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:

               1. Are pregnant or lactating.

               2. Have an asthma severity classification of severe persistent, using the NAEPP
                  classification, as evidenced by at least one of the following:

                    1. Require a dose of greater than 500 mcg of fluticasone per day or the
                       equivalent of another inhaled corticosteroid.

                    2. Have received more than 2 courses of oral or parenteral corticosteroids
                       within the last 12 months or one course within the last 3 months.

                    3. Have been treated with depot corticosteroids within the last 12 months.

                    4. Have been hospitalized for asthma within the 12 months prior to their
                       participation in Phase1b.

                    5. Have had an emergency room visit for asthma within the 3 months prior to
                       their participation in Phase 1b.

                    6. 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.

               3. Have received allergen immunotherapy (SLIT or SCIT) in the last 12 months prior
                  to their participation in Phase 1b.

               4. Have previously been treated with anti-IgE therapy in the 12 months prior to
                  their participation in Phase 1b.

               5. 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.

               6. Have received an investigational drug in the 30 days prior to their participation
                  in Phase 1b.

               7. 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.

               8. 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"

               9. 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:

          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 defined
             by the grading scale of Brown et al. for anaphylaxis and systemic reactions to study
             procedures.

          3. 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.

          4. 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:

               1. 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).

               2. Cannot perform spirometry at Screening.

               3. 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:

                    1. Require a dose of greater than 500mcg of fluticasone per day or the
                       equivalent of another inhaled corticosteroid.

                    2. Have received more than 2 courses of oral or parenteral corticosteroids
                       within the last 12 months or one course within the last 3 months.

                    3. Have been treated with depot corticosteroids within the last 12 months.

                    4. Have been hospitalized for asthma within the 12 months prior to recruitment.

                    5. Have had an emergency room visit for asthma within the 3 months prior to
                       recruitment.

                    6. 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.

               4. Have nasal polyps or other major structural abnormalities in their nasal cavities
                  as assessed by anterior rhinoscopy.

               5. 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.

               6. Do not have access to a phone (needed for scheduling appointments).

               7. 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.

               8. Have previously been treated with anti-IgE therapy in the 12 months prior to
                  recruitment.

               9. 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.

              10. Have received an investigational drug in the 30 days prior to recruitment or who
                  plan to use an investigational drug during the study.

              11. 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.