Clinical trial NCT03541187: Cockroach Immunotherapy in Children and Adolescents
Official title: Cockroach Immunotherapy in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Persistent Asthma
Keywords: cockroach
immunotherapy
inner city asthma
subcutaneous immunotherapy (SCIT)
Nasal Allergen Challenge (NAC)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Inner-City Asthma Consortium
name: Rho Federal Systems Division, Inc.
First posted: 2018-05-30
Enrollment: 82
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo
timeFrame: After 12 months
Secondary outcomes:
measure: Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment.
timeFrame: After 12 months
measure: Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo
timeFrame: After 12 months
measure: Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo
timeFrame: After 12 months
measure: Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo
timeFrame: After 12 months
measure: Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo
timeFrame: After 12 months
Other outcomes:
measure: EXPLORATORY: Composite Asthma Severity Score (CASI)-by Treatment Group
timeFrame: Month 10, Month 12
measure: EXPLORATORY: Number of Days With Asthma Symptoms-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Number of Nights With Asthma Symptoms-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Number of Days With Albuterol Use-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Number of Nights With Albuterol use-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Asthma Treatment step-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Number of Asthma exacerbations-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Spirometry Measurement: Forced Expiratory Volume in 1 Second (FEV1)-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Comparison of Rhinitis Symptom severity-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Comparison of Rhinitis Treatment step-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in German Cockroach-Specific Serum IgG Over Time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in German Cockroach-Specific Component Allergens Over time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in Cockroach Skin Test Reactivity Over Time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in Cockroach-Specific Blocking Antibodies Over Time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in Cockroach-Specific T Cell Response-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in Peripheral Blood Mononuclear Cells (PBMCs) Gene Expression Response to Cockroach (CR) Stimulation Over Time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
measure: EXPLORATORY: Change in Nasal Lavage Gene Expression Over Time-by Treatment Group
timeFrame: Baseline (Pre-treatment) through Study Completion, an Average of 1 Year
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center - IMPACT DC
state: District of Columbia
city: Chicago
country: United States
facility: Ann and Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System: Division of Allergy and Immunology
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital: Allergy, Immunology and Pulmonary Medicine Program
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical School
state: Texas
Study officials:
affiliation: Johns Hopkins Children's Center: Department of Allergy & Immunology
name: Robert Wood, MD
role: STUDY_CHAIR
affiliation: Henry Ford Health System: Division of Allergy and Immunology
name: Edward M. Zoratti, MD
role: STUDY_CHAIR
References: