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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

Tracking Information
First Submitted Date  ICMJE February 3, 2016
First Posted Date  ICMJE February 8, 2016
Last Update Posted Date June 26, 2020
Actual Study Start Date  ICMJE June 2016
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • 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)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 3, 2016)
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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
Official Title  ICMJE Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Immunologic Desensitization
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Allergen
    Subjects will be administered either Timothy Grass or Short Ragweed sublingual allergen tablets, depending on their individual allergic sensitization.
    Intervention: Drug: Allergen
  • Placebo Comparator: Placebo
    Subjects will be administered placebo sublingual tablets
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: February 3, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02676765
Other Study ID Numbers  ICMJE HM20006291
MISP 52707 ( Other Grant/Funding Number: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lawrence B Schwartz, M.D.,Ph.D. Virginia Commonwealth University
PRS Account Virginia Commonwealth University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP