Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy

Phase 3

Terminated

• Conditions: Immunologic Desensitization
• Interventions: Drug: allergen extract tablet; Drug: Placebo tablet

• Registration Number: NCT02676765
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

The purpose of this study is to determine if sublingual allergen immunotherapy tablets work by inducing a state of desensitization in mast cells and basophils.

Detailed Description

To induce clinical tolerance, a failure to respond to an allergen to which one was previously responsive, is an important objective for physicians, one that plays a significant role in the primary prevention of allergic reactions in the clinical practice of Allergy \& Immunology. The tolerance resulting after standard subcutaneous immunotherapy to aeroallergen and insect venom allergens is long lasting and allergen-specific, and may involve antigen-specific T regulatory cells. In contrast, tolerance resulting from drug desensitization protocols is short-lived, and postulated to target mast cells and basophils. Research into the cellular and biochemical processes by which desensitization occurs has revealed that mast cells desensitized to one antigen in vitro, under certain conditions, lose the ability to degranulate to unrelated antigens or to direct FcεRI cross-linking. Preliminary data suggests that this cross-desensitization can happen in patients undergoing incremental desensitization, depending in part on the percentage of IgE targeted to the allergen used for desensitization. This proposal therefore aims to explore desensitization and cross-desensitization in human volunteers undergoing standard sublingual (SL) immunotherapy to grass or ragweed pollen.

Subjects will undergo SL immunotherapy with either Timothy or Short Ragweed tablets, taking one tablet per day, or will take a placebo tablet. Titration skin testing to Timothy or Short Ragweed, to one or preferably two additional allergens to which the subject is sensitive, and to codeine as a control for mast cell activation capability through a non-IgE-dependent pathway will be performed to determine the PC3 value (see below). Skin testing, including histamine and diluent controls, will be performed prior to and at one and four weeks after initiation of immunotherapy. At each time point, blood will be obtained to measure total and antigen-specific IgE levels, tryptase and cytokine levels, and basophil activation with the relevant allergens and C5a as a non-IgE-mediated control for basophil activation.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-02-03
• Study First Submitted QC: 2016-02-03
• Study First Posted: 2016-02-08
• Study Start: 2016-06
• Primary Completion: 2018-01-18
• Study Completion: 2018-01-18
• Disposition First Submitted: 2021-07-19
• Disposition First Submitted QC: 2021-07-19
• Disposition First Posted: 2021-07-23
• Status Verified: 2022-02
• Results First Submitted: 2022-02-21
• Results First Submitted QC: 2022-02-21
• Last Update Submitted: 2022-02-21
• Results First Posted: 2022-03-18
• Last Update Posted: 2022-03-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

• Verified allergic sensitivity to either Timothy Grass or Short Ragweed pollen (primary allergen)
• Verified allergic sensitivity to at least one allergen in addition to the primary allergen

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Exclusion Criteria

• Negative skin testing to Timothy Grass or Short Ragweed pollen and at least one other environmental allergen
• Dermatographism
• Severe dermatologic condition that may interfere with skin testing
• Pregnancy
• H1 receptor antihistamine taken within 7 days of testing
• Systemic steroids
• Omalizumab taken at any time in the past
• Receiving or received allergen immunotherapy
• Desensitized to any drug within 6 months
• Current uncontrolled or severe asthma
• Eosinophilic esophagitis
• Significant pulmonary, cardiovascular, renal, hepatobiliary, or neurological diseases, or another disease process felt to put a subject at increased risk for adverse events
• Hypersensitivity to any of the inactive ingredients in the allergen extract tablets
• History of mental illness or drug or alcohol abuse that could interfere with the ability to comply with study requirements
• Inability or unwillingness to give written informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sublingual allergen tablets	allergen extract tablet	Subjects will be administered a sublingual allergen tablet customized to their individual allergic sensitization.
Placebo	Placebo tablet	Subjects will be administered placebo sublingual tablets

Primary Outcome Measures

Name	Time	Method
Change in PC3	Assessed at 2 weeks and at the end of the study (2 months)	Change in the dose of allergen eliciting a wheal 3 mm greater than negative control upon skin prick testing (PC3)
Change in Basophil Activation	Assessed at 2 weeks and at the end of the study (2 months)	Change in the dose of allergen eliciting a 50% increase in number of basophils positive for CD63 and/or CD203c relative to negative and positive controls

Secondary Outcome Measures

Name	Time	Method
Cross-desensitization - PC3	Assessed at 2 weeks and at the end of the study (2 months)	Change in the dose of an unrelated allergen eliciting a wheal 3 mm greater than negative control upon skin prick testing (PC3)
Cross-desensitization - Basophil Activation	Assessed at 2 weeks and at the end of the study (2 months)	Change in the dose of allergen eliciting a 50% increase in number of basophils positive for CD63 and/or CD203c relative to negative and positive controls

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States