Development of Cockroach Immunotherapy by the Inner-City Asthma Consortium

Phase 1

Completed

Conditions: Asthma
Perennial Allergic Rhinitis

Interventions: Biological: German cockroach (Blattella germanica) allergenic extract

Registration Number: NCT01221285

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: This trial is a biomarker-based pilot study of the safety of Cockroach Subcutaneous Immunotherapy in Cockroach-sensitive Adults (SCITCO) who have a history of perennial allergic rhinitis, asthma, or both.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Have a history of perennial allergic rhinitis, asthma, or both, for a minimum of 1 year 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:
- a forced expiratory volume at one second (FEV1) greater than or equal to 80% predicted value with or without controller medication
- 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 (Blattella germanica) cockroach allergenic extract
Are 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)
Are unable to perform spirometry 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 (SLIT or SCIT) in the last 12 months prior to recruitment or who plan to initiate or resume allergen immunotherapy during the study. Subjects who only received placebo therapy in the BioCSI protocol (A Biomarker-based Pilot Study of Cockroach Sublingual Immunotherapy in Cockroach Sensitive Adults With Asthma and/or Perennial Allergic Rhinitis, ICAC-12, NCT00829985) are eligible to participate in this 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
Refuse to sign the Epinephrine Auto-injector Training Form
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 as defined in the protocol
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 (either oral or topical route[s] of administration)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
German cockroach allergenic extract	German cockroach (Blattella germanica) allergenic extract	Participants will receive weekly escalating doses of glycerinated German cockroach allergenic extract administered via the subcutaneous route up to a Maximum Study Dose of 0.6 mL of extract at a concentration of 1:20 wt/vol.

Primary Outcome Measures

Name	Time	Method
Number of Reported Treatment-related Adverse Events (AEs)	Baseline through 6-months of treatment	Number of non-serious adverse events reported as possibly related, probably related, or definitely related to study participation.
Number of Reported Treatment-related Serious Adverse Events (SAEs)	Baseline through 6-months of treatment	Number of SAEs reported as possibly related, probably related, or definitely related to study participation.

Secondary Outcome Measures

Name	Time	Method
Change in German Cockroach-Specific Serum IgG Over Time	Baseline through 6-months of treatment	Outcome is the ratio of geometric means for baseline German cockroach-specific serum Immunoglobulin G (IgG) vs. post-baseline German cockroach-specific serum IgG. Numerator is geometric mean post-baseline IgG; denominator is baseline IgG.This result is an indicator of immune modulation over time, however its clinical significance is unclear.
Change in German Cockroach-Specific Serum IgE Over Time	Baseline through 6-months of treatment	Outcome is the ratio of geometric means for baseline German cockroach-specific serum Immunoglobulin E (IgE) vs. post-baseline German cockroach-specific serum IgE. Numerator is geometric mean post-baseline IgE; denominator is baseline IgE. This result is an indicator of immune modulation over time, however its clinical significance is unclear.
Change in German Cockroach-Specific Serum IgG4 Over Time	Baseline through 6-months of treatment	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. Numerator is geometric mean post-baseline IgG4; denominator is baseline IgG4. This result is an indicator of immune modulation over time, however its clinical significance is unclear.
Change in IgE Fragment Antibody Binding (FAB) Activity (10 Micrograms/mL Cockroach Allergen Extract)	Baseline through 6-months of treatment	Outcome is the change in mean IgE fragment antibody binding (FAB) activity, baseline to post-baseline. Serum from cockroach subcutaneous immunotherapy (SCIT)-treated participants were analyzed to determine if treatment inhibits the in-vitro cockroach antigen binding to B-cells after 6-months of treatment with cockroach SCIT, using the per protocol allergenic extract doses. This result is an indicator of immune modulation over time, however its clinical significance is unclear.