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Immunological Comparison of AIT and SCIT Immunotherapy Against Grass Pollen

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ClinicalTrials.gov Identifier: NCT01889875
Recruitment Status : Completed
First Posted : July 1, 2013
Last Update Posted : July 1, 2013
Sponsor:
Collaborator:
ALK-Abelló A/S
Information provided by (Responsible Party):
Vibeke Backer, Bispebjerg Hospital

Tracking Information
First Submitted Date  ICMJE June 24, 2013
First Posted Date  ICMJE July 1, 2013
Last Update Posted Date July 1, 2013
Study Start Date  ICMJE November 2010
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2013)
  • Changes over time in specific Antibodies [ Time Frame: 0, 1, 2, 3, 6, 7, 10, 12, and 15 months post treatment start ]
    IgE, IgG4
  • Changes over time in Basophil Activation Test [ Time Frame: 0, 1, 3, 6, 7, 10, 12, and 15 months post treatment start ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2013)
Changes over time in Nasal Challenge symptoms [ Time Frame: 0, 3, 10, and 15 months post treatment start ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunological Comparison of AIT and SCIT Immunotherapy Against Grass Pollen
Official Title  ICMJE Immunological Comparison of AIT and SCIT Immunotherapy Against Grass Pollen
Brief Summary Treatment of pollen allergies can be roughly divided into symptomatic treatment (e.g. antihistamines, steroids) and potentially curative immunotherapy. Immunotherapy can be delivered using subcutaneous or oral (mucosal) routes, with similar clinical outcome. The study seeks to compare immunological changes during subcutaneous (SCIT) and sublingual tablet (AIT) immunotherapy of grass pollen allergy (hayfever).
Detailed Description

Worldwide, more than 400 million people have allergic rhinitis, and sick-leave due to this condition costs societies billions of dollars annually1. Allergic rhinitis is most commonly treated with oral antihistamines and intranasal corticosteroids2. For moderate-severe rhinitis with poor control on topical treatment, immunotherapy should be considered3. Allergen immunotherapy is the only disease-modifying treatment available for IgE mediated allergy.

Immunotherapy is most commonly administered with subcutaneous injections of SQ-standardized allergen extracts (SCIT) and to a lesser extent, as sublingual drops (SLIT). However, other options now exist with the newly developed sublingual allergen immunotherapy tablets (AIT). The clinical effect of AIT4 and SCIT5 against grass pollen allergy has been demonstrated in large double-blind-placebo-controlled registration trials. These studies report significant reductions of symptom scores (AIT 30%, SCIT 32%) and seasonal rescue medication scores (AIT 38%, SCIT 41%) when compared with placebo4,5, persisting several years after withdrawal4,6. Immunotherapy may prevent new sensitizations and progression of rhinitis to asthma7-11. Allergen immunotherapy is generally well tolerated with few side effects, although a potential risk of anaphylactic reactions exists 12. A review of recent parallel meta-analyses on immunotherapy for grass pollen rhinitis suggests that the safety profile of AIT is superior to that of SCIT13.

The recommended length of immunotherapy with both SCIT and AIT is 3-5 years2, although the route of administration and the doses of allergen differ substantially. SCIT involves an up-dosing phase lasting 12-15 weeks with one or more weekly injections of increasing doses of allergen followed by a maintenance dose every 6-10 weeks. AIT starts with the daily maintenance dose, resulting in high cumulative doses. It is largely unknown whether the immunological mechanisms involved in the clinical effect are the same.

The changes in immunology have been extensively investigated for SCIT, and the most pronounced patterns are: 1) the induction of blocking antibodies, 2) a shift in Th1/Th2 balance towards Th1, and 3) induction of regulatory T cells. Similar mechanisms seem to be in play for AIT 14-16. Increases in allergen-specific non-IgE antibodies have been demonstrated in large trials of both SCIT and AIT treatment17,18, and studies have demonstrated that serum antibodies can reduce in vitro reactions mimicking allergic responses, such as IgE binding to allergen, IgE facilitated antigen presentation and basophil activation19-22, suggesting that both humoral and cellular effects play a role23.

The aim of the present study was to compare the effect of AIT and SCIT on antibody titers (IgE and IgG4), on allergen-IgE interaction in competition assays (IgE-blocking factor and FAP inhibition) and on effector cell activation (BAT). Nasal challenges were included to assess the changes in nasal response to grass pollen allergen.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Allergic Rhinitis Due to Grass Pollens
Intervention  ICMJE
  • Drug: ALK Grazax 75,000 SQ-T "Phleum pratense"
  • Drug: ALK AluTard 225 "Phleum pratense"
Study Arms  ICMJE
  • No Intervention: Control group
  • Active Comparator: Subcutaneous Immunotherapy (SCIT)
    Treatment using ALK AluTard 225 "Phleum pratense"
    Intervention: Drug: ALK AluTard 225 "Phleum pratense"
  • Active Comparator: Sublingual Allergen Immunotherapy Tablets (AIT)
    Treatment using ALK Grazax 75,000 SQ-T "Phleum pratense"
    Intervention: Drug: ALK Grazax 75,000 SQ-T "Phleum pratense"
Publications * Aasbjerg K, Backer V, Lund G, Holm J, Nielsen NC, Holse M, Wagtmann VR, Würtzen PA. Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy. Clin Exp Allergy. 2014 Mar;44(3):417-28.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2013)
40
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • history of rhinitis with hay fever symptoms during the grass pollen season,
  • a skin-prick-test-verified grass pollen allergy (Phleum pratense),
  • eligibility for immunotherapy based on ARIA guidelines

Exclusion Criteria:

  • current long-term systemic steroid treatment,
  • previous immunotherapy,
  • asthma and outside-season airway hyperresponsiveness (AHR) (September 2011),
  • pregnancy,
  • negative RAST for grass, and
  • treatment side effect
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01889875
Other Study ID Numbers  ICMJE Graesallergi
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vibeke Backer, Bispebjerg Hospital
Study Sponsor  ICMJE Bispebjerg Hospital
Collaborators  ICMJE ALK-Abelló A/S
Investigators  ICMJE Not Provided
PRS Account Bispebjerg Hospital
Verification Date June 2013

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