Immunologic DesensitizationPhase 3NCT02676765
Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
A Phase 3 study testing allergen extract tablet in people with Immunologic Desensitization, run by Virginia Commonwealth University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Immunologic Desensitization
- What is being tested?
- allergen extract tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 18 Jan 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
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.
Read the 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.
- Conditions
- Immunologic Desensitization
- Being tested
- allergen extract tablet, Placebo tablet
- Keywords
- Allergic rhinitis, Immunotherapy, Allergen, Sublingual Immunotherapy
- Medical subject headings
- Rhinitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allergen extract tabletDrug
Also called Ragwitek, Grastek
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
Placebo tabletDrug
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 group | Role | What they receive |
|---|---|---|
| sublingual allergen tablets | Experimental | Subjects will be administered a sublingual allergen tablet customized to their individual allergic sensitization. Receives: Drug: allergen extract tablet |
| Placebo | Placebo comparator | Subjects will be administered placebo sublingual tablets Receives: Drug: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PC3
Change in the dose of allergen eliciting a wheal 3 mm greater than negative control upon skin prick testing (PC3)
Measured: Assessed at 2 weeks and at the end of the study (2 months)
Change in Basophil Activation
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
Measured: Assessed at 2 weeks and at the end of the study (2 months)
Secondary outcomes (2)
Cross-desensitization - PC3
Change in the dose of an unrelated allergen eliciting a wheal 3 mm greater than negative control upon skin prick testing (PC3)
Measured: Assessed at 2 weeks and at the end of the study (2 months)
Cross-desensitization - Basophil Activation
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
Measured: Assessed at 2 weeks and at the end of the study (2 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2016 (estimated)
- Study startJun 2016
- Primary completion18 Jan 2018
- Study completion18 Jan 2018
Why it stopped: Intellectual property issues with drug manufacture.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Immunologic DesensitizationStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lawrence B Schwartz, M.D.,Ph.D., Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02676765
- Sponsor's protocol ID
- HM20006291
- Other IDs
- MISP 52707
- Status last verified
- Feb 2022
- First submitted
- 3 Feb 2016
- Last updated
- 18 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 22009002Maloney J, Bernstein DI, Nelson H, Creticos P, Hebert 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.
PubMed 24468255Creticos PS, Maloney J, Bernstein DI, Casale T, Kaur A, Fisher R, Liu N, Murphy K, Nekam 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.
PubMed 23622121Cockcroft 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. doi: 10.1111/j.1398-9995.2004.00612.x.
PubMed 15575931Niederberger V, Laffer S, Froschl 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. doi: 10.1016/s0091-6749(98)70391-4.
PubMed 9500760
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Desensitization and Cross-Desensitization During Oral Grass or Ragweed Pollen Immunotherapy
- ClinicalTrials.gov ID
- NCT02676765
- Acronym / sponsor ID
- HM20006291
- Conditions
- Immunologic Desensitization
- Keywords
- Allergic rhinitis, Immunotherapy, Allergen, Sublingual Immunotherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Intellectual property issues with drug manufacture.
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- 18 Jan 2018 (actual)
- Study completion
- 18 Jan 2018 (actual)
- First posted
- 8 Feb 2016 (estimated)
- Results
- Posted 18 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sublingual allergen tablets | Experimental | Drug: allergen extract tabletSubjects will be administered a sublingual allergen tablet customized to their individual allergic sensitization. |
| Placebo | Placebo comparator | Drug: Placebo tabletSubjects will be administered placebo sublingual tablets |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| allergen extract tabletAlso: Ragwitek, Grastek1 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 | Drug | sublingual allergen tablets |
| Placebo tablet1 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 | Drug | Placebo |
Primary outcome
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 number of basophils positive for CD63 and/or CD203c relative to negative and positive controls
2 secondary outcomes
Cross-desensitization - PC3
Time frame: Assessed at 2 weeks and at the end of the study (2 months)
Cross-desensitization - Basophil Activation
Time frame: Assessed at 2 weeks and at the end of the study (2 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22009002Zhao 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.
- Background: PubMed 24468255Maloney J, Bernstein DI, Nelson H, Creticos P, Hebert 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.
- Background: PubMed 23622121Creticos PS, Maloney J, Bernstein DI, Casale T, Kaur A, Fisher R, Liu N, Murphy K, Nekam 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.
- Background: PubMed 15575931Cockcroft 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. doi: 10.1111/j.1398-9995.2004.00612.x.
- Background: PubMed 9500760Niederberger V, Laffer S, Froschl 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. doi: 10.1016/s0091-6749(98)70391-4.
- Individual participant dataSharing planned: No
Related trials for Immunologic Desensitization
Active, not recruitingPhase 1/2
Carfilzomib and Belatacept for Desensitization
Highly Sensitized Prospective Kidney Transplant Recipients
Not yet recruiting
Oral Immunotherapy for Children With Peanut Allergy
Peanut Allergic Subjects, Peanut Allergies
Not yet recruiting
Oral Immunotherapy for Children With Egg Allergy
Egg Allergy, Egg Hypersensitivity
Not yet recruitingPhase 2
UNC Cashew Sublingual Immunotherapy
Cashew Nut Allergy, Tree Nut Allergies
Active, not recruitingPhase 2
GRK-Biased Activation Via β2-Adrenergic Receptors in Human Skeletal Muscle
Overweight and Obesity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence B Schwartz, M.D.,Ph.D. principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing allergen extract tablet in people with Immunologic Desensitization, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in PC3 (time frame: Assessed at 2 weeks and at the end of the study (2 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02676765, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2022.