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

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ClinicalTrials.gov Identifier: NCT02676765
Recruitment Status : Suspended (Intellectual property issues with drug manufacture.)
First Posted : February 8, 2016
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Immunologic Desensitization Drug: Allergen Drug: Placebo Not Applicable

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
Actual Study Start Date : June 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Allergen
Subjects will be administered either Timothy Grass or Short Ragweed sublingual allergen tablets, depending on their individual allergic sensitization.
 Drug: Allergen
1 allergen extract tablet, placed under the tongue until dissolved, taken daily; do not swallow for 1 minute after placing tablet; do not eat or drink for 5 minutes after placing tablet
Other Names:
  • Ragwitek
  • Grastek
Placebo Comparator: Placebo
Subjects will be administered placebo sublingual tablets
 Drug: Placebo
1 placebo tablet, placed under the tongue until dissolved, taken daily; do not swallow for 1 minute after placing tablet; do not eat or drink for 5 minutes after placing tablet


Outcome Measures
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Primary Outcome Measures :
  1. Change in PC3 [ Time Frame: 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)

  2. Change in Basophil Activation [ Time Frame: Assessed at 2 weeks and at the end of the study (2 months) ]
    Change in the dose of allergen eliciting a 50% increase in CD63 and/or CD203c expression relative to negative and positive controls


Secondary Outcome Measures :
  1. Cross-desensitization - PC3 [ Time Frame: 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)

  2. Cross-desensitization - Basophil Activation [ Time Frame: Assessed at 2 weeks and at the end of the study (2 months) ]
    Change in the dose of an unrelated allergen eliciting a 50% increase in CD63 and/or CD203c expression relative to negative and positive controls


Other Outcome Measures:
  1. Percent Allergen-specific IgE [ Time Frame: Assessed at enrollment, at 2 weeks, and at the end of the study (2 months) ]
    The percent of total serum IgE that is specific for the primary allergen will be compared to the degree (if any) of cross-desensitization seen by skin prick or basophil activation testing


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02676765


Locations
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United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
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Principal Investigator: Lawrence B Schwartz, M.D.,Ph.D. Virginia Commonwealth University
More Information
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Publications:

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02676765    
Other Study ID Numbers: HM20006291
MISP 52707 ( Other Grant/Funding Number: Merck )
First Posted: February 8, 2016    Key Record Dates
Last Update Posted: June 26, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Virginia Commonwealth University:
Allergic rhinitis
Immunotherapy, Allergen
Sublingual Immunotherapy