Persistent Asthma
Conditions
Keywords
cockroach, immunotherapy, inner city asthma, subcutaneous immunotherapy (SCIT), Nasal Allergen Challenge (NAC)
Brief summary
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
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.
Interventions
BIOLOGICALGerman cockroach allergenic extract
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).
BIOLOGICALPlacebo for German cockroach allergenic extract
Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Sponsors
Inner-City Asthma Consortium
Rho Federal Systems Division, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | After 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | After 12 months | Summary tables will present the total number of Immunotherapy related adverse event within the course of treatment. |
| Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | After 12 months | 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. |
| Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | After 12 months | 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. |
| Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo | After 12 months | 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. |
| Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo | After 12 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EXPLORATORY: Asthma Treatment step-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Defined by medication requirements for asthma control. |
| EXPLORATORY: Number of Asthma exacerbations-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the study. |
| EXPLORATORY: Spirometry Measurement: Forced Expiratory Volume in 1 Second (FEV1)-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | FEV1 is air volume exhaled in 1 second during spirometry and is a measure of asthma severity. |
| EXPLORATORY: Comparison of Rhinitis Treatment step-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Defined by medication requirements for rhinitis control. |
| EXPLORATORY: Change in German Cockroach-Specific Serum IgG Over Time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | 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. |
| EXPLORATORY: Comparison of Rhinitis Symptom severity-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Measured using the Modified Rhinitis Symptom Utility Index. |
| EXPLORATORY: Change in Cockroach Skin Test Reactivity Over Time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | As a measure of response to cockroach immunotherapy. |
| EXPLORATORY: Change in Cockroach-Specific Blocking Antibodies Over Time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | To explore serum measurement(s) of in-vitro cockroach antigen binding to B-cells. |
| EXPLORATORY: Change in Cockroach-Specific T Cell Response-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Limited to Part A only: Peripheral blood mononuclear cells (PBMCs) will be evaluated for the magnitude and phenotype of the Cockroach (CR)-specific T cell response to CR immunotherapy. |
| EXPLORATORY: Change in Peripheral Blood Mononuclear Cells (PBMCs) Gene Expression Response to Cockroach (CR) Stimulation Over Time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | To identify the changes in PBMC gene expression response to cockroach stimulation over time and compare those changes between the treated (German cockroach allergenic extract ) and untreated (placebo) group. |
| EXPLORATORY: Change in Nasal Lavage Gene Expression Over Time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | To identify the changes in nasal lavage gene expression response to cockroach stimulation over time and compare those changes between the treated (German cockroach allergenic extract ) and untreated (placebo) group. |
| EXPLORATORY: Change in German Cockroach-Specific Component Allergens Over time-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Including but not limited to the following component allergens: Bla g 1, Bla g 2, Bla g 4, Bla g 5 and Per a 7. |
| EXPLORATORY: Composite Asthma Severity Score (CASI)-by Treatment Group | Month 10, Month 12 | The Composite Asthma Severity Index (CASI) is a comprehensive severity scale combining multiple facets of asthma severity: impairment, risk, and treatment. The CASI score ranges from 0 to 20 points, with higher scores indicating higher levels of severity, and includes 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. |
| EXPLORATORY: Number of Days With Asthma Symptoms-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Defined by the presence of wheezing or tightness in the chest, or cough. |
| EXPLORATORY: Number of Nights With Asthma Symptoms-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Defined by participant waking up during the night due to the presence of wheezing or tightness in the chest, or cough. |
| EXPLORATORY: Number of Days With Albuterol Use-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Albuterol is a bronchodilator used for asthma control. |
| EXPLORATORY: Number of Nights With Albuterol use-by Treatment Group | Baseline (Pre-treatment) through Study Completion, an Average of 1 Year | Albuterol is a bronchodilator used for asthma control. |
Countries
United States
Participant flow
Recruitment details
Recruited 308 participants with the goal of enrolling 80 participants into this trial. Each participant received a 12 month treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cockroach SCIT Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm.
-In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional 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.
German cockroach allergenic extract: 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). | 28 |
| Placebo Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm.
-In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional 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.
Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%). | 29 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | >2 bursts of systemic corticosteroids for asthma during treatment period (Starting Nov 2020) | 1 | 2 |
| Overall Study | Did not meet randomization criteria | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 6 |
| Overall Study | Moved out of town | 1 | 0 |
| Overall Study | Need for dose >500 mcg of fluticasone for 6 months | 0 | 1 |
| Overall Study | Potential inability to tolerate maintenance dose | 1 | 0 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | Cockroach SCIT | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 2.48 | 12.2 years STANDARD_DEVIATION 2.49 | 12.1 years STANDARD_DEVIATION 2.46 |
| Age, Customized ≥ 12 years | 16 Participants | 18 Participants | 34 Participants |
| Age, Customized Between 8 and 11 years | 12 Participants | 11 Participants | 23 Participants |
| Annual household income (<15k) Dont Know | 1 Participants | 0 Participants | 1 Participants |
| Annual household income (<15k) No | 15 Participants | 13 Participants | 28 Participants |
| Annual household income (<15k) Yes | 12 Participants | 16 Participants | 28 Participants |
| Caretaker completed high school No | 5 Participants | 6 Participants | 11 Participants |
| Caretaker completed high school Yes | 23 Participants | 23 Participants | 46 Participants |
| Cockroach-specific IgE at Baseline | 7.9 kUA/L | 2.6 kUA/L | 4.6 kUA/L |
| Cockroach-specific IgG4 at Baseline | 35.0 ng/mL | 35.0 ng/mL | 35.0 ng/mL |
| NAC responsive dose at baseline Reactive Dose 1 at NAC Baseline - 0 mcg/mL | 0 Participants | 0 Participants | 0 Participants |
| NAC responsive dose at baseline Reactive Dose 2 at NAC Baseline - 0.00492 mcg/mL | 2 Participants | 2 Participants | 4 Participants |
| NAC responsive dose at baseline Reactive Dose 3 at NAC Baseline - 0.0155 mcg/mL | 3 Participants | 3 Participants | 6 Participants |
| NAC responsive dose at baseline Reactive Dose 4 at NAC Baseline - 0.0490 mcg/mL | 1 Participants | 1 Participants | 2 Participants |
| NAC responsive dose at baseline Reactive Dose 5 at NAC Baseline - 0.155 mcg/mL | 4 Participants | 2 Participants | 6 Participants |
| NAC responsive dose at baseline Reactive Dose 6 at NAC Baseline - 0.489 mcg/mL | 5 Participants | 6 Participants | 11 Participants |
| NAC responsive dose at baseline Reactive Dose 7 at NAC Baseline - 1.54 mcg/mL | 6 Participants | 3 Participants | 9 Participants |
| NAC responsive dose at baseline Reactive Dose 8 at NAC Baseline - 4.88 mcg/mL | 3 Participants | 9 Participants | 12 Participants |
| NAC responsive dose at baseline Reactive Dose 9 at NAC Baseline - 15.4 mcg/mL | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 16 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 7 Participants |
| Region of Enrollment United States | 28 participants | 29 participants | 57 participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 42 |
| other Total, other adverse events | 34 / 40 | 35 / 42 |
| serious Total, serious adverse events | 2 / 40 | 0 / 42 |
Outcome results
Primary
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.
Time frame: After 12 months
Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cockroach SCIT | Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | -1.02 score on a scale | Standard Error 0.37 |
| Placebo | Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | -0.79 score on a scale | Standard Error 0.35 |
p-value: 0.6395% CI: [-1.15, 0.7]ANCOVA
Secondary
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.
Time frame: After 12 months
Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 2 at 12 Months -0.00492 mcg/mL | 1 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 6 at 12 Months - 0.489 mcg/mL | 4 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 4 at 12 Months - 0.0490 mcg/mL | 3 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 7 at 12 Months - 1.54mcg/mL | 1 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 3 at 12 Months - 0.0155mcg/mL | 1 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 8 at 12 Months - 4.88 mcg/mL | 1 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 5 at 12 Months - 0.155 mcg/mL | 1 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 9 at 12 Months - 15.4 mcg/mL | 14 Participants |
| Cockroach SCIT | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 1 at 12 Months - 0 mcg/mL | 2 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 9 at 12 Months - 15.4 mcg/mL | 10 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 1 at 12 Months - 0 mcg/mL | 0 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 2 at 12 Months -0.00492 mcg/mL | 0 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 3 at 12 Months - 0.0155mcg/mL | 3 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 4 at 12 Months - 0.0490 mcg/mL | 1 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 5 at 12 Months - 0.155 mcg/mL | 4 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 6 at 12 Months - 0.489 mcg/mL | 1 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 7 at 12 Months - 1.54mcg/mL | 7 Participants |
| Placebo | Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo | Reactive Dose 8 at 12 Months - 4.88 mcg/mL | 3 Participants |
p-value: 0.5195% CI: [0.42, 1.54]Regression, Cox
Secondary
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.
Time frame: After 12 months
Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cockroach SCIT | Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | -0.65 score on a scale | Standard Error 0.33 |
| Placebo | Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo | -0.48 score on a scale | Standard Error 0.31 |
p-value: 0.6995% CI: [-0.99, 0.66]ANCOVA
Secondary
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.
Time frame: After 12 months
Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cockroach SCIT | Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo | -0.56 Log(kuA/L) | Standard Error 0.2 |
| Placebo | Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo | -0.53 Log(kuA/L) | Standard Error 0.19 |
p-value: 0.9195% CI: [-0.54, 0.49]ANCOVA
Secondary
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.
Time frame: After 12 months
Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cockroach SCIT | Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo | -1.58 Log(ng/mL) | Standard Error 0.22 |
| Placebo | Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo | -6.90 Log(ng/mL) | Standard Error 0.21 |
p-value: <0.00195% CI: [4.77, 5.87]ANCOVA
Secondary
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.
Time frame: After 12 months
Population: All participants who sign consent and undergo study procedures at Screening.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cockroach SCIT | Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | Number of Immunotherapy Related Adverse Events | 130 Adverse Events |
| Cockroach SCIT | Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | Number of Immunotherapy Related Serious Adverse Events | 0 Adverse Events |
| Placebo | Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | Number of Immunotherapy Related Adverse Events | 36 Adverse Events |
| Placebo | Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. | Number of Immunotherapy Related Serious Adverse Events | 0 Adverse Events |
Other Pre-specified
EXPLORATORY: Asthma Treatment step-by Treatment Group
Defined by medication requirements for asthma control.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in Cockroach Skin Test Reactivity Over Time-by Treatment Group
As a measure of response to cockroach immunotherapy.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in Cockroach-Specific Blocking Antibodies Over Time-by Treatment Group
To explore serum measurement(s) of in-vitro cockroach antigen binding to B-cells.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in Cockroach-Specific T Cell Response-by Treatment Group
Limited to Part A only: Peripheral blood mononuclear cells (PBMCs) will be evaluated for the magnitude and phenotype of the Cockroach (CR)-specific T cell response to CR immunotherapy.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in German Cockroach-Specific Component Allergens Over time-by Treatment Group
Including but not limited to the following component allergens: Bla g 1, Bla g 2, Bla g 4, Bla g 5 and Per a 7.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in German Cockroach-Specific Serum IgG Over Time-by Treatment Group
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 (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in Nasal Lavage Gene Expression Over Time-by Treatment Group
To identify the changes in nasal lavage gene expression response to cockroach stimulation over time and compare those changes between the treated (German cockroach allergenic extract ) and untreated (placebo) group.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Change in Peripheral Blood Mononuclear Cells (PBMCs) Gene Expression Response to Cockroach (CR) Stimulation Over Time-by Treatment Group
To identify the changes in PBMC gene expression response to cockroach stimulation over time and compare those changes between the treated (German cockroach allergenic extract ) and untreated (placebo) group.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Comparison of Rhinitis Symptom severity-by Treatment Group
Measured using the Modified Rhinitis Symptom Utility Index.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Comparison of Rhinitis Treatment step-by Treatment Group
Defined by medication requirements for rhinitis control.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Composite Asthma Severity Score (CASI)-by Treatment Group
The Composite Asthma Severity Index (CASI) is a comprehensive severity scale combining multiple facets of asthma severity: impairment, risk, and treatment. The CASI score ranges from 0 to 20 points, with higher scores indicating higher levels of severity, and includes 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations.
Time frame: Month 10, Month 12
Other Pre-specified
EXPLORATORY: Number of Asthma exacerbations-by Treatment Group
Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the study.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Number of Days With Albuterol Use-by Treatment Group
Albuterol is a bronchodilator used for asthma control.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Number of Days With Asthma Symptoms-by Treatment Group
Defined by the presence of wheezing or tightness in the chest, or cough.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Number of Nights With Albuterol use-by Treatment Group
Albuterol is a bronchodilator used for asthma control.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Number of Nights With Asthma Symptoms-by Treatment Group
Defined by participant waking up during the night due to the presence of wheezing or tightness in the chest, or cough.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Other Pre-specified
EXPLORATORY: Spirometry Measurement: Forced Expiratory Volume in 1 Second (FEV1)-by Treatment Group
FEV1 is air volume exhaled in 1 second during spirometry and is a measure of asthma severity.
Time frame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year