Biomarker-based Cockroach Sublingual Immunotherapy Study (BioCSI) - Full Text View

Purpose

There is currently no effective way to prevent development of allergic rhinitis (nasal allergies) and asthma and no cure. Sublingual immunotherapy (SLIT), a type of therapy in which allergens are placed under the tongue, may be a way to control and possibly prevent allergic rhinitis and asthma. However, detailed research of this approach is limited. The purpose of this study is to evaluate the safety and efficacy of a sublingual cockroach extract given to adults with perennial allergic rhinitis, asthma, or both.

Condition	Intervention	Phase
Rhinitis, Allergic, Perennial Asthma	Biological: Glycerinated German Cockroach Allergenic Extract Biological: Placebo	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Biomarker-based Pilot Study of Cockroach Sublingual Immunotherapy in Cockroach Sensitive Adults With Asthma and/or Perennial Allergic Rhinitis (ICAC-12)

Resource links provided by NLM:

MedlinePlus related topics: Allergy Asthma

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Difference in German Cockroach-Specific Serum IgE Over Time [ Time Frame: Baseline through 6-months of treatment ] [ Designated as safety issue: No ]
Outcome is the ratio of geometric means for baseline German cockroach-specific serum Immunoglobulin E (IgE) vs. post-baseline German cockroach-specific serum IgE. This result is an indicator of immune modulation over time, however its clinical significance is unclear.

Secondary Outcome Measures:

Difference in German Cockroach-Specific Serum IgG4 Over Time [ Time Frame: Baseline through 6-months of treatment ] [ Designated as safety issue: No ]
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. This ratio is an indicator of immune modulation, however its clinical significance is unclear.
Change in IgE Fragment Antibody Binding (FAB) Activity (30 Micrograms/mL Cockroach Allergen Extract) [ Time Frame: Baseline through 6-months of treatment ] [ Designated as safety issue: No ]
Outcome is the change in mean IgE fragment antibody binding (FAB) activity, baseline to post-baseline. Serum from sensitized donor incubated with 30 micrograms/mL of cockroach allergen extract in presence or absence of equal volume of sera from study participants to assess allergen-IgE binding. (Presence of sera from those who previously received allergen-specific immunotherapy, viz., study participants post-baseline, expected to inhibit allergen-IgE complex binding.) This change is an indicator of immune modulation, however its clinical significance is unclear.
Change in IgE Fragment Antibody Binding (FAB) Activity (60 Micrograms/mL Cockroach Allergen Extract) [ Time Frame: Baseline through 6-months of treatment ] [ Designated as safety issue: No ]
Outcome is the change in mean IgE fragment antibody binding (FAB) activity, baseline to post-baseline. Serum from sensitized donor incubated with 60 micrograms/mL of cockroach allergen extract in presence or absence of equal volume of sera from study participants to assess allergen-IgE binding. (Presence of sera from those who previously received allergen-specific immunotherapy, viz., study participants post-baseline, expected to inhibit allergen-IgE complex binding.) This change is an indicator of immune modulation, however its clinical significance is unclear.
Percent of Participants With the Occurrence of Adverse Events (AE) [ Time Frame: Participant enrollment to end of study (up to 6 months post-baseline) ] [ Designated as safety issue: Yes ]
Percent of participants who experienced at least one adverse event

Enrollment:	54
Study Start Date:	January 2009
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Glycerinated German Cockroach Allergenic Extract Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered concentrated (1:20 weight per volume [w/v]) daily doses of glycerinated German cockroach allergenic extract (50% glycerin) placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The extract was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Biological: Glycerinated German Cockroach Allergenic Extract Concentrated (1:20 w/v) daily doses of glycerinated German cockroach allergenic extract placed under the tongue to dissolve. The extract is also administered during the preliminary dosing visits in up to five escalating doses or until the maximum study dose (420 microliters, 1:20 w/v) is achieved.
Placebo Comparator: Placebo Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered daily doses of placebo placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The placebo was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 weight per volume [w/v]) was achieved.	Biological: Placebo Daily doses of cockroach allergenic extract placebo placed under the tongue to dissolve

Arms

Assigned Interventions

Experimental: Glycerinated German Cockroach Allergenic Extract

Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered concentrated (1:20 weight per volume [w/v]) daily doses of glycerinated German cockroach allergenic extract (50% glycerin) placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The extract was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.

Biological: Glycerinated German Cockroach Allergenic Extract

Concentrated (1:20 w/v) daily doses of glycerinated German cockroach allergenic extract placed under the tongue to dissolve. The extract is also administered during the preliminary dosing visits in up to five escalating doses or until the maximum study dose (420 microliters, 1:20 w/v) is achieved.

Placebo Comparator: Placebo

Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered daily doses of placebo placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 6 months. Note: The placebo was also administered during the preliminary dosing visits, up to five escalating doses, or until the maximum study dose (420 microliters, 1:20 weight per volume [w/v]) was achieved.

Biological: Placebo

Daily doses of cockroach allergenic extract placebo placed under the tongue to dissolve

Detailed Description:

Over the last two decades, the prevalence of asthma has dramatically increased in many parts of the world. Currently, there are no effective ways to prevent the development of nasal allergies and asthma, and there are no cures for these diseases. Sublingual immunotherapy (SLIT) may help reduce symptoms of allergy and asthma. The purpose of this study is to evaluate the safety and efficacy of a cockroach extract given sublingually to adults with perennial (year-round) nasal allergies, asthma, or both.

At study entry, participants will receive a dose of placebo and then up to five incremental doses of cockroach extract or placebo at 15-minute intervals while observed by the clinical research staff. Doses will continue to be given until a sign or symptom occurs that indicates the participant is having difficulty tolerating the drug, or until the maximum study dose is reached.

For the next 6 months, participants will take the maximum study dose of cockroach extract or placebo daily at home.

This study will consist of 8 study visits. Skin tests, breathing tests, and blood collection will occur at study screening and other visits during the study. At study entry, participants will be taught to use an EpiPen in the event of a severe allergic reaction at any time during the study. A physical and oral exam, breathing test, and blood collection will occur at study entry and all follow-up visits.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

History of perennial allergic rhinitis, asthma, or both for a minimum of 1 year prior to study entry
Positive skin prick test to German cockroach
No known contraindications to therapy with glycerinated German cockroach allergenic extract or placebo
Willing to sign the written Informed Consent prior to initiation of any study procedures

Exclusion Criteria:

Cannot perform spirometry at screening
Have clinically significant abnormal laboratory values
Have an Asthma classification of severe persistent at screening.
Hospitalized for asthma within the 6 months prior to study entry
Life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within the 2 years prior to study entry
No access to a telephone
Received allergen immunotherapy within the last 12 months prior to study entry and plan on initiating or resuming immunotherapy during the study
Treatment with anti-immunoglobulin E (anti-IgE) therapy within 1 year of study entry
Received an investigational drug within the 30 days prior to study entry and plan on using an investigational drug during the study
Experienced nausea, vomiting, abdominal pain or cramps, or diarrhea within the 3 months prior to study entry
Refuse to sign the Epinephrine Auto-injector Training Form
Does not primarily speak english
Plan to move from the area during the study period
History of idiopathic anaphylaxis or anaphylaxis grade 3
Using tricyclic antidepressants or beta-adrenergic blocker drugs
Clinically unacceptable complete blood count (CBC) and liver function tests, as defined by a hemoglobin less than 11.5 in males and 10.0 in females, or platelet counts less than 150,000 and an Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) greater than twice the upper limit of normal
Any condition that, in the opinion of the investigator, would interfere with the study
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829985

Locations

United States, Colorado
National Jewish Center
Denver, Colorado, United States, 80206
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Inner-City Asthma Consortium

Investigators

Study Chair:

Robert Wood, MD

Johns Hopkins University

More Information

Publications:

Ciprandi G, Contini P, Pistorio A, Murdaca G, Puppo F. Sublingual immunotherapy reduces soluble HLA-G and HLA-A,-B,-C serum levels in patients with allergic rhinitis. Int Immunopharmacol. 2008 Dec 16; [Epub ahead of print]

Passalacqua G, Pawankar R, Baena-Cagnani CE, Canonica GW. Sublingual immunotherapy: where do we stand? Present and future. Curr Opin Allergy Clin Immunol. 2009 Feb;9(1):1-3. No abstract available.

Rolland JM, Gardner LM, O'Hehir RE. Allergen-related approaches to immunotherapy. Pharmacol Ther. 2008 Dec 7; [Epub ahead of print]

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00829985 History of Changes
Other Study ID Numbers:	DAIT ICAC-12, BioCSI
Study First Received:	January 26, 2009
Results First Received:	January 31, 2013
Last Updated:	March 11, 2013
Health Authority:	United States: Food and Drug Administration

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

Rhinitis, Allergic, Perennial
Rhinitis, Allergic, Seasonal
Immunotherapy

Asthma
Nasal Allergies
Hypersensitivity

Additional relevant MeSH terms:

Asthma
Rhinitis
Rhinitis, Allergic, Perennial
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases

Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on May 23, 2013