Asthma, Perennial Allergic Rhinitis
Conditions
Keywords
Cockroach, Immunotherapy, Subcutaneous immunotherapy, Inner city asthma
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.
Interventions
BIOLOGICALGerman cockroach (Blattella germanica) allergenic extract
Participants received 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.
Sponsors
Inner-City Asthma Consortium
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glycerinated German Cockroach Allergenic Extract Participants received 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. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Glycerinated German Cockroach Allergenic Extract |
|---|---|
| Age, Continuous | 37.5 years |
| German Cockroach-Specific Serum Immunoglobulin E (IgE) Levels | 3.8 kU/L |
| Glycerinated German Cockroach Prick Skin Test Wheal Size | 6.8 mm |
| Participants with Asthma | 7 participants |
| Participants with Perennial Allergic Rhinitis | 6 participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Number of Reported Treatment-related Adverse Events (AEs)
Number of non-serious adverse events reported as possibly related, probably related, or definitely related to study participation.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Moderate, Definitely | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Severe, Definitely | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Severe, Probably | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Severe, Possibly | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Moderate , Probably | 3 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Moderate , Possibly | 1 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Mild , Definitely | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Mild Probably | 47 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Adverse Events (AEs) | Mild Possibly | 99 Events |
Primary
Number of Reported Treatment-related Serious Adverse Events (SAEs)
Number of SAEs reported as possibly related, probably related, or definitely related to study participation.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Serious Adverse Events (SAEs) | Definitely related | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Serious Adverse Events (SAEs) | Probably related | 0 Events |
| Glycerinated German Cockroach Allergenic Extract | Number of Reported Treatment-related Serious Adverse Events (SAEs) | Possibly related | 0 Events |
Secondary
Change 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. 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.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Change in German Cockroach-Specific Serum IgE Over Time | 1.8 Ratio | 95% Confidence Interval 0.1 |
p-value: 0.0295% CI: [1.1, 2.8]Fold change
Secondary
Change 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. 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.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Change in German Cockroach-Specific Serum IgG4 Over Time | 12.9 Ratio | 95% Confidence Interval 0.7 |
p-value: <0.000195% CI: [7.5, 22.5]Fold Change
Secondary
Change in German Cockroach-Specific Serum IgG Over Time
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.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Change in German Cockroach-Specific Serum IgG Over Time | 2.5 Ratio | 95% Confidence Interval 0.1 |
p-value: <0.000195% CI: [1.8, 3.4]Fold change
Secondary
Change in IgE Fragment Antibody Binding (FAB) Activity (10 Micrograms/mL Cockroach Allergen Extract)
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.
Time frame: Baseline through 6-months of treatment
Population: Intent-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycerinated German Cockroach Allergenic Extract | Change in IgE Fragment Antibody Binding (FAB) Activity (10 Micrograms/mL Cockroach Allergen Extract) | -42.8 Percent antibody binding | Standard Error 8.3 |
p-value: <0.000195% CI: [-59.4, -26.2]Change