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

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

Tracking Information

• First Submitted Date: February 3, 2016
• First Posted Date: February 8, 2016
• Last Update Posted Date: June 26, 2020
• Actual Study Start Date: June 2016
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
• Official Title: 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: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Immunologic Desensitization

Intervention

• 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

• 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 *

• Zhao W, Gomez G, Macey M, Kepley CL, Schwartz LB. In vitro desensitization of human skin mast cells. J Clin Immunol. 2012 Feb;32(1):150-60. doi: 10.1007/s10875-011-9605-8. Epub 2011 Oct 19.
• Maloney J, Bernstein DI, Nelson H, Creticos P, Hébert J, Noonan M, Skoner D, Zhou Y, Kaur A, Nolte H. Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol. 2014 Feb;112(2):146-153.e2. doi: 10.1016/j.anai.2013.11.018. Epub 2013 Dec 21.
• Creticos PS, Maloney J, Bernstein DI, Casale T, Kaur A, Fisher R, Liu N, Murphy K, Nékám K, Nolte H. Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults. J Allergy Clin Immunol. 2013 May;131(5):1342-9.e6. doi: 10.1016/j.jaci.2013.03.019.
• Cockcroft DW, Davis BE, Boulet LP, Deschesnes F, Gauvreau GM, O'Byrne PM, Watson RM. The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen. Allergy. 2005 Jan;60(1):56-9.
• Niederberger V, Laffer S, Fröschl R, Kraft D, Rumpold H, Kapiotis S, Valenta R, Spitzauer S. IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Bet v 2) account for a high percentage of grass pollen-specific IgE. J Allergy Clin Immunol. 1998 Feb;101(2 Pt 1):258-64.

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: February 3, 2016): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02676765
• Other Study ID Numbers: HM20006291; MISP 52707 ( Other Grant/Funding Number: Merck )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Virginia Commonwealth University
• Study Sponsor: Virginia Commonwealth University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lawrence B Schwartz, M.D.,Ph.D.; Virginia Commonwealth University

• PRS Account: Virginia Commonwealth University
• Verification Date: June 2020