Biomarkers of Cockroach Sublingual Immunotherapy 2 (BioCSI-2)

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Perennial Allergic Rhinitis
• Intervention / Treatment: Biological: Cockroach Sublingual Immunotherapy (SLIT) - Low Dose; Other: Placebo; Biological: Cockroach Sublingual Immunotherapy (SLIT) - High Dose

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a history of perennial allergic rhinitis, asthma, or both, before study entry. For those with asthma:

  1. 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
  2. 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:

  1. requires 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
  3. have been treated with depot steroids within the last 12 months
  4. have been hospitalized for asthma within the 6 months prior to recruitment
  5. 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:

  1. nausea or vomiting
  2. abdominal pain or cramps severe enough to interfere with daily activities (excluding those associated with menstruation).
  3. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cockroach Sublingual Immunotherapy (SLIT) - Low Dose; 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; 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.; Other Names: Blattella germanica
Placebo Comparator: Placebo; 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; 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.; Other Names: German cockroach (Blattella germanica) placebo
Experimental: Cockroach Sublingual Immunotherapy (SLIT) - High Dose; 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; 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.; Other Names: Blattella germanica

What is the study measuring?

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)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Wood RA, Togias A, Wildfire J, Visness CM, Matsui EC, Gruchalla R, Hershey G, Liu AH, O'Connor GT, Pongracic JA, Zoratti E, Little F, Granada M, Kennedy S, Durham SR, Shamji MH, Busse WW. Development of cockroach immunotherapy by the Inner-City Asthma Consortium. J Allergy Clin Immunol. 2014 Mar;133(3):846-52.e6. doi: 10.1016/j.jaci.2013.08.047. Epub 2013 Nov 1.

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): June 11, 2014
• Last Update Submitted That Met QC Criteria: June 5, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: immunotherapy; cockroach; sublingual immunotherapy (SLIT); inner city asthma
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Asthma; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Physiological Effects of Drugs; Immunologic Factors
• Other Study ID Numbers: DAIT ICAC-17