Biomarker-based Cockroach Sublingual Immunotherapy Study (BioCSI)

Study Overview
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Brief Summary
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There is currently no effective way to prevent development of allergic rhinitis (nasal allergies) and asthma and no cure. Sublingual immunotherapy (SLIT), a type of therapy in which allergens are placed under the tongue, may be a way to control and possibly prevent allergic rhinitis and asthma. However, detailed research of this approach is limited. The purpose of this study is to evaluate the safety and efficacy of a sublingual cockroach extract given to adults with perennial allergic rhinitis, asthma, or both.

Detailed Description
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Over the last two decades, the prevalence of asthma has dramatically increased in many parts of the world. Currently, there are no effective ways to prevent the development of nasal allergies and asthma, and there are no cures for these diseases. Sublingual immunotherapy (SLIT) may help reduce symptoms of allergy and asthma. The purpose of this study is to evaluate the safety and efficacy of a cockroach extract given sublingually to adults with perennial (year-round) nasal allergies, asthma, or both. At study entry, participants will receive a dose of placebo and then up to five incremental doses of cockroach extract or placebo at 15-minute intervals while observed by the clinical research staff. Doses will continue to be given until a sign or symptom occurs that indicates the participant is having difficulty tolerating the drug, or until the maximum study dose is reached. For the next 6 months, participants will take the maximum study dose of cockroach extract or placebo daily at home. This study will consist of 8 study visits. Skin tests, breathing tests, and blood collection will occur at study screening and other visits during the study. At study entry, participants will be taught to use an EpiPen in the event of a severe allergic reaction at any time during the study. A physical and oral exam, breathing test, and blood collection will occur at study entry and all follow-up visits.

Official Title
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A Biomarker-based Pilot Study of Cockroach Sublingual Immunotherapy in Cockroach Sensitive Adults With Asthma and/or Perennial Allergic Rhinitis (ICAC-12)

Conditions
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Rhinitis, Allergic, Perennial, Asthma

Intervention / Treatment
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* Biological: Glycerinated German Cockroach Allergenic Extract
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of perennial allergic rhinitis, asthma, or both for a minimum of 1 year prior to study entry; Positive skin prick test to German cockroach; No known contraindications to therapy with glycerinated German cockroach allergenic extract or placebo; and Willing to sign the written Informed Consent prior to initiation of any study procedures. Exclusion Criteria: Cannot perform spirometry at screening; Have clinically significant abnormal laboratory values; Have an Asthma classification of severe persistent at screening; Hospitalized for asthma within the 6 months prior to study entry; Life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within the 2 years prior to study entry; No access to a telephone; Received allergen immunotherapy within the last 12 months prior to study entry and plan on initiating or resuming immunotherapy during the study; Treatment with anti-immunoglobulin E (anti-IgE) therapy within 1 year of study entry; Received an investigational drug within the 30 days prior to study entry and plan on using an investigational drug during the study; Experienced nausea, vomiting, abdominal pain or cramps, or diarrhea within the 3 months prior to study entry; Refuse to sign the Epinephrine Auto-injector Training Form; Does not primarily speak English; Plan to move from the area during the study period; History of idiopathic anaphylaxis or anaphylaxis grade 3; Using tricyclic antidepressants or beta-adrenergic blocker drugs; Clinically unacceptable complete blood count (CBC) and liver function tests, as defined by a hemoglobin less than 11.5 in males and 10.0 in females, or platelet counts less than 150,000 and an Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) greater than twice the upper limit of normal; Any condition that, in the opinion of the investigator, would interfere with the study; or Pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glycerinated German Cockroach Allergenic Extract<br>Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered concentrated (1:20 weight per volume [w/v]) daily doses of glycerinated German cockroach allergenic extract (50% glycerin) placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The extract was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved. | Biological: Glycerinated German Cockroach Allergenic Extract<br>* Concentrated (1:20 w/v) daily doses of glycerinated German cockroach allergenic extract placed under the tongue to dissolve. The extract is also administered during the preliminary dosing visits in up to five escalating doses or until the maximum study dose (420 microliters, 1:20 w/v) is achieved.<br>|
| Placebo Comparator: Placebo<br>Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered daily doses of placebo placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The placebo was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 weight per volume [w/v]) was achieved. | Biological: Placebo<br>* Daily doses of cockroach allergenic extract placebo placed under the tongue to dissolve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in German Cockroach-Specific Serum IgE Over Time | Outcome is the ratio of geometric means for baseline German cockroach-specific serum Immunoglobulin E (IgE) vs. 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 6-months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in German Cockroach-Specific Serum IgG4 Over Time | Outcome is the ratio of geometric means for baseline German cockroach-specific serum Immunoglobulin subclass 4 (IgG4) vs. post-baseline German cockroach-specific serum IgG4. This ratio is an indicator of immune modulation, however its clinical significance is unclear. | Baseline through 6-months of treatment | 
| Change in IgE Fragment Antibody Binding (FAB) Activity (30 Micrograms/mL Cockroach Allergen Extract) | Outcome is the change in mean IgE fragment antibody binding (FAB) activity, baseline to post-baseline. Serum from sensitized donor incubated with 30 micrograms/mL of cockroach allergen extract in presence or absence of equal volume of sera from study participants to assess allergen-IgE binding. (Presence of sera from those who previously received allergen-specific immunotherapy, viz., study participants post-baseline, expected to inhibit allergen-IgE complex binding.) This change is an indicator of immune modulation, however its clinical significance is unclear. | Baseline through 6-months of treatment | 
| Change in IgE Fragment Antibody Binding (FAB) Activity (60 Micrograms/mL Cockroach Allergen Extract) | Outcome is the change in mean IgE fragment antibody binding (FAB) activity, baseline to post-baseline. Serum from sensitized donor incubated with 60 micrograms/mL of cockroach allergen extract in presence or absence of equal volume of sera from study participants to assess allergen-IgE binding. (Presence of sera from those who previously received allergen-specific immunotherapy, viz., study participants post-baseline, expected to inhibit allergen-IgE complex binding.) This change is an indicator of immune modulation, however its clinical significance is unclear. | Baseline through 6-months of treatment | 
| Percent of Participants With the Occurrence of Adverse Events (AE) | Percent of participants who experienced at least one adverse event | Participant enrollment to end of study (up to 6 months post-baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinitis, Allergic, Perennial, Rhinitis, Allergic, Seasonal, Immunotherapy, Asthma, Nasal Allergies, Hypersensitivity