Biomarkers of Cockroach Sublingual Immunotherapy 2

Study Overview
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Brief Summary
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This trial is a follow-up study of the ICAC-12 Phase I/II trial (NCT00829985), and is designed to study biomarkers of the immune response to allergen immunotherapy and the safety of this therapy in a pediatric population.

Detailed Description
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Over the past two decades, scientific evidence has shown that the combination of cockroach allergy and cockroach exposure is one of the most important factors contributing to the dramatic increase in asthma morbidity seen in inner city children with asthma. Therefore, a major goal of the National Institute of Allergy and Infectious Diseases (NIAID) Inner City Asthma Consortium (ICAC) is ultimately to conduct a large multi-center trial of cockroach sublingual immunotherapy (SLIT) in inner-city asthma. As a step toward achieving this goal, ICAC is conducting a clinical trial comparing two doses of glycerinated German cockroach (Blattella germanica) allergenic extract to placebo, administered under the tongue (sublingual).

Official Title
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A Biomarker-Based Pilot Study of Cockroach Sublingual Immunotherapy in Cockroach Sensitive Children With Asthma and/or Perennial Allergic Rhinitis

Conditions
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Asthma, Perennial Allergic Rhinitis

Intervention / Treatment
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* Biological: Cockroach Sublingual Immunotherapy (SLIT) - Low Dose
* Other: Placebo
* Biological: Cockroach Sublingual Immunotherapy (SLIT) - High Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a history of perennial allergic rhinitis, asthma, or both, before study entry. For those with asthma: a diagnosis of asthma will be defined as a report by the participant that they have had a clinical diagnosis of asthma made by a physician over a year ago the participant's asthma must be well controlled as defined by: ii. a forced expiratory volume at one second (FEV1) greater than or equal to 80% predicted value with or without controller medication ii. albuterol use for no more than 3 days per week in each of the previous 2 weeks for asthma symptoms (not including exercise prophylaxis) Are sensitive to German cockroach (Blattella germanica) as documented by a positive (>/=3 mm greater than negative control) skin prick test result and detectable German cockroach specific IgE (>/=0.35 kUA/L) Have no known contraindications to therapy with glycerinated German cockroach allergenic extract or placebo Parent or legally authorized representative (LAR) of child is willing to sign the written Informed Consent prior to initiation of any study procedure Exclusion Criteria: Are pregnant or lactating. 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 or peak flow at screening Have an asthma severity classification at recruitment of severe persistent, using the National Asthma Education and Prevention Program (NAEPP) classification, as evidenced by at least one of the following: requires 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 have been treated with depot steroids within the last 12 months have been hospitalized for asthma within the 6 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 Do not have access to a phone (needed for scheduling appointments) Have received allergen immunotherapy 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 within 1 year of recruitment Have received an investigational drug in the 30 days prior to recruitment or who plan to use an investigational drug during the study Have in the last 3 months prior to recruitment experienced on average >/=1 day per week any of the symptoms below: nausea or vomiting abdominal pain or cramps severe enough to interfere with daily activities (excluding those associated with menstruation). diarrhea Refuse to sign the Epinephrine Auto-injector Training Form Participants who meet any of the following criteria are not eligible for enrollment and may not be reassessed. Participants are ineligible if they: Do not primarily speak English Plan to move from the area during the study period Have a history of idiopathic anaphylaxis or anaphylaxis grade 2 or higher 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 patient (e.g., gastrointestinal disease, gastroesophageal reflux disease, chronic infections, scleroderma, hepatic, and gallbladder disease) Are using tricyclic antidepressants or beta-adrenergic blocker drugs (either oral and/or topical route[s] of administration)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cockroach Sublingual Immunotherapy (SLIT) - Low Dose<br>Glycerinated German cockroach (Blatella germanica) allergen extract administered sublingually with a maximally tolerated dose of 420 microliters daily | Biological: Cockroach Sublingual Immunotherapy (SLIT) - Low Dose<br>* Participants are randomized to receive daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume [w/v] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.<br>* Other names: Blattella germanica;|
| Placebo Comparator: Placebo<br>Placebo administered sublingually not to exceed the maximally tolerated dose of either 1.) 420 microliters daily (placebo - low dose randomization) or 2.) 840 microliters twice daily (placebo - high dose randomization) | Other: Placebo<br>* Participants are randomized to receive either daily (low dose) or twice-daily (high dose) placebo treatment placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume [w/v]) was achieved.<br>* Other names: German cockroach (Blattella germanica) placebo;|
| Experimental: Cockroach Sublingual Immunotherapy (SLIT) - High Dose<br>Glycerinated German cockroach (Blatella germanica) allergen extract administered sublingually with a maximally tolerated dose of 840 microliters taken twice daily | Biological: Cockroach Sublingual Immunotherapy (SLIT) - High Dose<br>* Participants are randomized to receive twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume [w/v] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.<br>* Other names: Blattella germanica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in German Cockroach-Specific Serum IgE Over Time | Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum IgE. This result is an indicator of immune modulation over time, however its clinical significance is unclear. | Baseline through 3 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in German Cockroach-Specific Serum IgG Over Time | Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum immunoglobulin G (IgG). This result is an indicator of immune modulation over time, however its clinical significance is unclear. | Baseline through 3 months of treatment | 
| Change in German Cockroach-Specific Serum IgG4 Over Time | Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum immunoglobulin subclass 4 (IgG4). This result is an indicator of immune modulation over time, however its clinical significance is unclear. | Baseline through 3 months of treatment | 
| Change in IgE Fragment Antibody Binding (FAB) Activity Over Time | Outcome is change in mean IgE FAB activity level from baseline to post-baseline (status post 3 months of treatment). Serum from cockroach sublingual immunotherapy (SLIT)-treated participants were analyzed to determine if treatment inhibits in-vitro cockroach SLIT, using the per protocol allergenic extract doses. This result is an indicator of immune modulation over time, however its clinical significance is unclear.(Reference: Shamji MH et al. The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods 2006;317(1-2): 71-9). | Baseline through 3 months of treatment | 
| Percent of Participants With the Occurrence of Adverse Events (AEs) | Percent of participants who experienced at least one AE. | Participant enrollment to end of study (up to 3 months post-baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cockroach, immunotherapy, sublingual immunotherapy (SLIT), inner city asthma