Cockroach Immunotherapy in Children and Adolescents (CRITICAL)

• ClinicalTrials.gov Identifier: NCT03541187
• Recruitment Status: Recruiting
• First Posted: May 30, 2018
• Last Update Posted: January 26, 2021
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Inner-City Asthma Consortium; Rho Federal Systems Division, Inc.
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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 asthma severity can be improved by cockroach subcutaneous immunotherapy (SCIT) treatment.

Condition or disease	Intervention/treatment	Phase
Persistent Asthma	Biological: German cockroach allergenic extract; Biological: Placebo for German cockroach allergenic extract	Phase 2

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

The study will occur in two parts - Part A and Part B:

- Part A will enroll 80 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.

An interim analysis will be conducted when all Part A participants have completed their 12-month NAC. If an effect is seen for the Part A NAC analysis, the study will proceed to Part B.

-Part B will enroll 220 participants 6 to 16 years of age, who are sensitized to cockroach and have asthma. A positive NAC will not be required for inclusion into Part B.

The study will be based on a continuous treatment schedule with German cockroach allergenic extract or placebo, up to a maximum of 36 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Cockroach Immunotherapy in Children and Adolescents
• Actual Study Start Date: July 16, 2018
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: G. cockroach allergenic extract - Part A; Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 14 years of age will be randomized to this treatment arm. An interim analysis will be conducted when all Part A participants have completed their 12-month NAC. If an effect is seen for the Part A NAC analysis, the study will proceed to Part B. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. After maintenance dose is achieved, participants will receive three 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 24 months and up to a maximum of 36 months.	Biological: 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).; Other Name: Blattella germanica allergenic extract
Placebo Comparator: Placebo- Part A; Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 14 years of age will be randomized to this treatment arm. An interim analysis will be conducted when all Part A participants have completed their 12-month NAC. If an effect is seen for the Part A NAC analysis, the study will proceed to Part B. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. Once the maintenance dose is achieved, participants will receive three 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 24 months and up to a maximum of 36 months.	Biological: 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%).; Other Name: Placebo for Blattella germanica allergenic extract
Experimental: G. cockroach allergenic extract-Part B; Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 110 participants 6 to 16 years of age who are sensitized to cockroach and have asthma will be randomized to this treatment arm. In contrast to Part A, a positive NAC will not be required for inclusion into Part B treatment. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. Once the maintenance dose is achieved, participants will receive three 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 24 months and up to a maximum of 36 months.	Biological: 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).; Other Name: Blattella germanica allergenic extract
Placebo Comparator: Placebo- Part B; Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 110 participants 6 to 16 years of age who are sensitized to cockroach and have asthma will be randomized to this treatment arm. In contrast to Part A treatment, a positive NAC will not be required for inclusion into Part B treatment. -Up to 2 doses of the assigned SCIT treatment will be given weekly during dose escalation, separated by a minimum of 2 days. Once the maintenance dose is achieved, participants will receive three 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 24 months and up to a maximum of 36 months.	Biological: 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%).; Other Name: Placebo for Blattella germanica allergenic extract

Outcome Measures

Primary Outcome Measures :

1. Composite Asthma Severity Index (CASI)-by Treatment Group [ Time Frame: 5 month outcome period between Month 19 and Month 24 (2 Years) of Treatment ]
   CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations.

Secondary Outcome Measures :

1. Rate of Related Adverse Events (AEs)-by Treatment Group [ Time Frame: Treatment Randomization through Study Completion, an Average of 2 Years ]
   Non-serious adverse events reported as possibly related, probably related, or definitely related to study participation.
2. Rate of Related Serious Adverse Events (SAEs)-by Treatment Group [ Time Frame: Treatment Randomization through Study Completion, an Average of 2 Years ]
   SAEs reported as possibly related, probably related, or definitely related to study participation.
3. Change in Total Nasal Symptom Score (TNSS)-by Treatment Group [ Time Frame: Baseline (Pre-treatment) to Month 24 (2 Years) ]
   TNSS is a sum of the nasal symptom score for sneezing, rhinorrhea, nasal congestion, and nasal itching. Each symptom is scored on a scale from 0 to 3; the range of sums for TNSS is 0 to 12. The analysis will compare the mean TNSS Area Under the Curve (AUC) at the follow-up Nasal Allergen Challenge (NAC).
4. Number of Days with Asthma Symptoms-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 years ]
   Defined by the presence of wheezing or tightness in the chest, or cough.
5. Number of Nights with Asthma Symptoms-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   Defined by participant waking up during the night due to the presence of wheezing or tightness in the chest, or cough.
6. Number of Days with Albuterol Use-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   Albuterol is a bronchodilator used for asthma control.
7. Number of nights with albuterol use-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   Albuterol is a bronchodilator used for asthma control.
8. Asthma treatment step-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   Defined by medication requirements for asthma control.
9. Number of Asthma exacerbations-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
10. Spirometry Measurement: Forced Expiratory Volume in 1 second (FEV1)-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
    FEV1 is air volume exhaled in 1 second during spirometry and is a measure of asthma severity.
11. Comparison of Rhinitis symptom severity-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
    Measured using the Modified Rhinitis Symptom Utility Index.
12. Comparison of Rhinitis treatment step-by Treatment Group [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
    Defined by medication requirements for rhinitis control.

Other Outcome Measures:

1. EXPLORATORY: Change in German Cockroach-Specific Serum IgE Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
2. EXPLORATORY: Change in German Cockroach-Specific Serum IgG Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
3. EXPLORATORY: Change in German Cockroach-Specific Serum IgG4 Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
4. EXPLORATORY: Change in German Cockroach-Specific Component Allergens Over time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
5. EXPLORATORY: Change in Cockroach-Specific Blocking Antibodies Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   To explore serum measurement(s) of in-vitro cockroach antigen binding to B-cells.
6. EXPLORATORY: Change in Cockroach Skin Test Reactivity Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   As a measure of response to cockroach immunotherapy.
7. EXPLORATORY: Change in Cockroach-Specific T cell Response [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
8. EXPLORATORY: Change in Peripheral Blood Mononuclear Cells (PBMCs) Gene Expression Response to Cockroach (CR) Stimulation Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.
9. EXPLORATORY: Change in Nasal Lavage Gene Expression Over Time [ Time Frame: Baseline (Pre-treatment) through Study Completion, an Average of 2 Years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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):

  • in Part A: 8 to 17 years of age
  • in Part B: 6 to 16 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.

• Has a history of persistent asthma, for a minimum of 1 year before study entry:

  • 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).
• Has no known contraindications to therapy with glycerinated German cockroach allergenic extract or placebo;
• In Part A only: Subject must 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 at screening; 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).

Contacts and Locations

Locations

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

Contact: Pascuala Pinedo-Estrada 720-777-8077 pascuala.pinedo-estrada@childrenscolorado.org

Principal Investigator: Andrew Liu, MD

United States, District of Columbia

Children's National Medical Center - IMPACT DC; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Alicia Newcomer 202-476-4698 anewcome@childrensnational.org

Principal Investigator: Stephen Teach, MD

United States, Illinois

Ann and Robert Lurie Children's Hospital of Chicago; Recruiting

Chicago, Illinois, United States, 60611

Contact: Sarah Godley 312-227-6454 sgodley@luriechildrens.org

Principal Investigator: Jacqueline Pongracic, MD

United States, Maryland

Johns Hopkins University; Recruiting

Baltimore, Maryland, United States, 21205

Contact: Michele Cootauco 410-614-5467 mcootaul@jhu.edu

Principal Investigator: Robert Wood, MD

United States, Massachusetts

Boston Medical Center; Recruiting

Boston, Massachusetts, United States, 02118

Contact: Nicole Gonzalez, BS 617-358-7626 Nicolegg@bu.edu

Contact: Edlira Gjerasi 617-414-3384 edgjeras@bu.edu

Principal Investigator: George T. O'Connor, MD, MS

United States, Michigan

Henry Ford Health System: Division of Allergy and Immunology; Recruiting

Detroit, Michigan, United States, 48202

Contact: Sherae Hereford 313-916-6954 sherefo3@hfhs.org

Principal Investigator: Edward Zoratti, MD

United States, Missouri

St. Louis Children's Hospital: Allergy, Immunology and Pulmonary Medicine Program; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: Beth Tesson 314-286-1290 Tesson_B@kids.wustl.edu

Principal Investigator: Leonard Bacharier, MD

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact: Michele Barry 212-824-7961 Michele.Barry@mountsinai.org

Principal Investigator: Paula J. Busse, MD

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

Contact: Yudy Fermamdez-pau 212-305-6250 yf2190@cumc.columbia.edu

Contact: Marcela Pierce 212-305-6255 mp2648@cumc.columbia.edu

Principal Investigator: Meyer Kattan, MD

United States, Ohio

Cincinnati Children's Hospital; Recruiting

Cincinnati, Ohio, United States, 45229-3039

Contact: Kristi Curtsinger 513-803-1651 kristi.curtsinger@cchmc.org

Principal Investigator: Carolyn Kercsmar, MD

Principal Investigator: Gurjit Hershey, MD

United States, Texas

University of Texas Southwestern Medical School; Recruiting

Dallas, Texas, United States, 75390-8859

Contact: Dolores Santoyo 214-648-2620 dolores.santoyo@utsouthwestern.edu

Principal Investigator: Rebecca Gruchalla, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Inner-City Asthma Consortium

Rho Federal Systems Division, Inc.

Investigators

• Study Chair: Robert Wood, MD; Johns Hopkins Children's Center: Department of Allergy & Immunology
• Study Chair: Edward M. Zoratti, MD; Henry Ford Health System: Division of Allergy and Immunology

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Division of Allergy, Immunology, and Transplantation (DAIT) 

Inner-City Asthma Consortium 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03541187
• Other Study ID Numbers: DAIT ICAC-28; ICAC-28 ( Other Identifier: Inner-City Asthma Consortium )
• First Posted: May 30, 2018
• Last Update Posted: January 26, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Participant level data access will be made available to the public at some point in the future via the mechanism of the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• Time Frame: The aim is to share data with the public within 24 months upon completion of the study.
• Access Criteria: ImmPort public data access.
• URL: http://www.immport.org/immport-open/public/home/home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

cockroach; immunotherapy; inner city asthma; subcutaneous immunotherapy (SCIT); Nasal Allergen Challenge (NAC)

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases