Cockroach Immunotherapy in Children and Adolescents

Study Overview
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Brief Summary
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Scientific evidence has shown that, over the past two decades, 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 Inner City Asthma Consortium (ICAC) is to evaluate the efficacy of cockroach immunotherapy in inner city asthma. The primary objective of the study is to determine if the response to nasal allergen challenge (NAC) will be changed with treatment with cockroach subcutaneous immunotherapy (SCIT) treatment.

Detailed Description
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This is a 1:1 randomized, double-masked (blind), placebo-controlled, multicenter trial with 2 treatment arms: German Cockroach Subcutaneous Immunotherapy (SCIT) + guideline-based standard asthma care, OR Placebo (for German Cockroach Subcutaneous Immunotherapy [SCIT]) + guideline-based standard asthma care Eighty participants 8 to 17 years of age who are sensitized to cockroach, have asthma, and a positive cockroach Nasal Allergen Challenge (NAC) before treatment randomization will be enrolled.

Official Title
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Cockroach Immunotherapy in Children and Adolescents

Conditions
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Persistent Asthma

Intervention / Treatment
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* Biological: German cockroach allergenic extract
* Biological: Placebo for German cockroach allergenic extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Subject(s) And/or parent guardian must be able to understand and provide informed consent; Age at date of recruitment (e.g., screening): 8 to 17 years of age Have a primary place of residence in one of the pre-selected recruitment census tracts (Reference: Inner-City Asthma Consortium): --Note: Subjects who do not live in the pre-selected census tracts but live within the Office of Management and Budget (OMB) defined Metropolitan Statistical Area and have publicly-funded health insurance will qualify for inclusion. Have a history of persistent asthma, for a minimum of 1 year before study entry: A diagnosis of asthma will be defined as a report by the caretaker that the subject had a clinical diagnosis of asthma made by a clinician ≥1 year ago, resulting in a prescription of preventative asthma medication, and Must have persistent asthma as defined by the current need for at least 88 mcg fluticasone (or the equivalent of another inhaled corticosteroid) to control asthma at the time of screening. At the time of randomization, the subject's asthma must be well controlled as defined by: A Forced Expiratory Volume in 1 second (FEV1) ≥80% predicted, and An Asthma Control Test (ACT) or Childhood Asthma Control Test (CACT) score ≥20. Is sensitive to German cockroach as documented by: a positive (≥3 mm greater than negative control) skin prick test result, and detectable German cockroach specific Immunoglobulin E (IgE) (≥ 0.35 kUA/L). Have no known contraindications to therapy with glycerinated German cockroach allergenic extract or placebo; Have a positive cockroach nasal challenge, as defined by reaching a Total Nasal Symptom Score (TNSS) of ≥6 or a sneezing score of 3 at dose 2 or above during the challenge before randomization; and Have documentation of current medical insurance with prescription coverage at randomization. Exclusion Criteria:Subject(s) Unable or unwilling to give written informed consent or comply with the study protocol; That is pregnant or lactating; That are post-menarcheal females must be abstinent or use a medically acceptable birth control method throughout their participation in the study (e.g. oral, subcutaneous, mechanical, or surgical contraception); That cannot perform spirometry and peak flow at treatment randomization; That have an asthma severity classification at the time of treatment randomization of severe persistent, using the The National Asthma Education and Prevention Program (NAEPP) classification, as evidenced by at least one of the following: Requires a dose >500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid, Has received more than 2 courses of oral or parenteral corticosteroids in the last 12 months or one course within the last 3 months prior to study entry, Has been treated with depot steroids within the 3 months prior to study entry, Has been hospitalized for asthma within the 6 months prior to study entry, or Has had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to study entry. Does not have access to a phone (needed for scheduling appointments); Has received allergen immunotherapy (Sublingual Immunotherapy [SLIT] or Subcutaneous Immunotherapy [SCIT]) in the last 12 months or, who plan to initiate or resume allergen immunotherapy during the study; Has received biologic therapy (e.g., anti-Immunoglobulin E [IgE], anti-IL-4, anti-IL-5) within 6 months of study entry; Has received an investigational drug in the 30 days prior to recruitment or who plan to use an investigational drug during the study; Has 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. Who have nasal polyps or other major structural abnormalities in their nasal cavities as assessed by anterior rhinoscopy, Who meet any of the following criteria are not eligible for enrollment and may not be reassessed: That plan to move from the area during the study period, Have a history of anaphylaxis grade 3 or higher as defined by World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System, 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 product or pose additional risk to the subject, 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. Are using tricyclic antidepressants or beta-adrenergic blocker drugs (both oral and topical).

Ages Eligible for Study
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Minimum Age: 8 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G. cockroach allergenic extract<br>Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 14 years of age will be randomized to this treatment arm. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. After maintenance dose is achieved, participants will receive three maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. | Biological: German cockroach allergenic extract<br>* Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).<br>* Other names: Blattella germanica allergenic extract;|
| Placebo Comparator: Placebo<br>Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 14 years of age will be randomized to this treatment arm. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. Once the maintenance dose is achieved, participants will receive three maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. | Biological: Placebo for German cockroach allergenic extract<br>* Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).<br>* Other names: Placebo for Blattella germanica allergenic extract;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | The study's primary endpoint is the mean TNSS change from baseline to 12 months, calculated as the difference between baseline and 12-month mean TNSS up to baseline responsive dose. TNSS (0-12) is the sum of three participant-assessed scores for rhinorrhea, congestion, itching, and staff-monitored sneezing, rated 0=None, 1=Mild, 2=Moderate, 3=Severe. Analysis uses ANCOVA modeling mean TNSS difference with factors for treatment arm, site, and baseline mean TNSS. Least square means (LSmeans), SEs, difference in LSmeans between treatment and placebo groups, 95% CI, and p-value are reported. A greater change in the LSmeans indicates a better outcome. | After 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | Summary tables will present the total number of Immunotherapy related adverse event within the course of treatment. | After 12 months | 
| Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | The Total Nasal Symptom Score (TNSS) Area under the curve (AUC) will be calculated separately at baseline and 12 months for each subject using the trapezoidal rule and divided by their baseline reactive dose. TNSS (0-12) is the sum of three participant-assessed scores for rhinorrhea, congestion, itching, and staff-monitored sneezing, rated 0=None, 1=Mild, 2=Moderate, 3=Severe. Analysis uses ANCOVA modeling AUC TNSS with factors for treatment arm, site, and baseline TNSS AUC. Least square means (LSmeans), SEs, difference in LSmeans between treatment and placebo groups, 95% CI, and p-value are reported. A greater change in the LSmeans indicates a better outcome. | After 12 months | 
| Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | The 12-month responsive dose is being calculated as the first dose that triggers a reaction of TNSS (Total Nasal Symptom Score) greater than or equal to 6 or a sneeze score of 3, whichever occurs first, in a sequence of up to 9 doses. To estimate the hazard ratio and 95% confidence interval, we are conducting an analysis using Cox regression with censoring, while controlling for the baseline responsive dose and site. Participants who do not experience a reaction before reaching the last dose will be considered right-censored. | After 12 months | 
| Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo | The difference in log-transformed German Cockroach-specific IgE between baseline and 12 months is being modeled using ANCOVA with factors for treatment arm, site, and the respective log-transformed IgE baseline as covariates. For each treatment group, we present least square means (LSmeans) and their associated standard errors (SEs). We report the difference in LSmeans between the treatment and placebo groups, along with the associated 95% confidence interval (CI) and p-value. | After 12 months | 
| Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo | The difference in log-transformed German Cockroach-specific IgG4 between baseline and 12 months is being modeled using ANCOVA with factors for treatment arm, site, and the respective log-transformed IgG4 baseline as covariates. For each treatment group, we present least square means (LSmeans) and their associated standard errors (SEs). We report the difference in LSmeans between the treatment and placebo groups, along with the associated 95% confidence interval (CI) and p-value. | After 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cockroach, immunotherapy, inner city asthma, subcutaneous immunotherapy (SCIT), Nasal Allergen Challenge (NAC)