Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Intervention: Grazax; Grazax Placebo
Intervention description: The active treatment arm will receive active grass pollen immunotherapy tablet (AIT), Grazax Oral Lyophilisate 75,000 SQ-T once daily.; This arm will receive Grazax placebo once daily which contains the same composition as in the active Grazax tablet with the only difference being the exclusion of the grass pollen allergen extract.
Intervention MeSH terms: Immunomodulating Agents; Immunologic Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: grass pollen allergy; hayfever; atopy; allergic rhinitis; sublingual immunotherapy tablets

Summary:

      About 45 million people in Europe have allergic rhinitis (hay fever) - inflammation of the
      nasal passages causing sneezing, runny nose, nasal congestion, itching and tearing of the
      eyes. In the United Kingdom (UK), seasonal hay fever due to grass pollen allergy accounts for
      approximately 7 times more doctors' appointments than asthma. The standard treatment for hay
      fever consists of treating the symptoms with a nasal spray and an antihistamine. However, in
      a survey taken in a UK general practice less than 40% of patients with hay fever reported
      good symptom control with this standard treatment. For those patients with hay fever whose
      symptoms are not well controlled by treatment with antihistamines and nasal sprays,
      subcutaneous immunotherapy (SCIT) - (monthly injections of a grass allergen extract for a
      period of 3-5 years) is an effective alternative, and is approved in the UK on a named
      patient basis. More recently, allergen immunotherapy tablets (AITs) have been developed,
      including grass pollen allergen tablets. These have been shown to be highly effective in the
      treatment of hay fever, with the additional benefit of being convenient for patients, given
      that they may be taken at home. Grazax® (manufactured by Allergologisk Laboratorium København
      (ALK)-Abello, Denmark) has UK and European Union (EU) license for use in the treatment of
      troublesome grass pollen induced hay fever. The aim of this research is to investigate the
      effects of the AIT treatment on the immune system over time - which changes are taking place
      and when in the course of treatment. This will provide insight into the complexities of the
      development of allergen-specific immune tolerance - how harmful allergic responses against
      innocuous substances such as grass pollen can be overridden.
    

Eligibility criteria:

        Atopic Participants:

        Inclusion Criteria:

          -  age 18 to 65

          -  grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak
             symptoms in May-July.

          -  moderate to severe rhinoconjunctivitis symptoms with or without mild seasonal asthma
             interfering with usual daily activities/sleep.

          -  rhinoconjunctivitis that remains troublesome despite treatment with either
             antihistamines or nasal corticosteroids during the grass pollen season.

          -  Positive skin prick test response (wheal diameter ≥ 3 mm) to timothy grass pollen.

          -  Positive specific immunoglobulin E (IgE), defined as IgE immunoCAP ≥ 0.7 Immuno Solid
             Phase Allergenchip (ISAC) standardized units (ISU), against timothy grass pollen.

          -  if applicable a negative urine pregnancy test and willingness to use an effective form
             of contraception for the duration of involvement in the study.

          -  The ability to give informed consent and comply with study procedures.

          -  A positive grass pollen nasal allergen challenge test as defined by a total nasal
             symptom score (TNSS) of at least 7/12 after 5 minutes with an allergen dose of 5,000
             bioequivalent units (BU)/ml.

        Exclusion Criteria:

          -  Previous grass pollen allergen immunotherapy.

          -  Prebronchodilator forced expiratory volume at one second (FEV1) < 70% of predicted
             value out of grass-pollen season.

          -  A clinical history of symptomatic allergic rhinitis and/or asthma caused by an
             allergen to which the participant is regularly exposed.

          -  Perennial asthma requiring regular inhaled corticosteroids.

          -  Seasonal symptoms outside the grass-pollen season.

          -  History of emergency visit or hospital admission for asthma in the previous 12 months.

          -  History of chronic obstructive pulmonary disease.

          -  History of significant recurrent acute sinusitis.

          -  History of chronic sinusitis.

          -  At screening visit evidence for upper respiratory tract infection.Participants may be
             re-evaluated for eligibility after symptoms resolve.

          -  Current smokers or a history of ≥ 5 pack years.

          -  History of life-threatening anaphylaxis or angioedema.

          -  Ongoing systemic immunosuppressive treatment.

          -  The use of any investigational drug within 30 days of the screening visit.

          -  The presence of any medical condition that the investigator deems incompatible with
             participation in the study.

          -  History of fish allergy with positive skin test and/or positive specific IgE test to
             vertebrate/finned fish.

          -  Contraindications taking Grazax.

        Non-Atopic:

        Inclusion Criteria:

          -  age 18 to 65.

          -  Negative skin prick test response to timothy grass pollen and panel of aeroallergens.

          -  Negative specific IgE, defined as IgE immunoCAP < 0.35 ISU, against timothy grass
             pollen.

          -  If applicable a negative urine pregnancy test at the time of screening and willingness
             to use an effective form of contraception for the duration of involvement in the
             study.

          -  The ability to give informed consent and comply with study procedures.

        Exclusion criteria:

          -  Previous grass pollen allergen immunotherapy.

          -  Prebronchodilator FEV1 < 70% of predicted value out of grass-pollen season.

          -  symptomatic allergic rhinitis and/or asthma caused by an allergen to which the
             participant is regularly and perennially exposed (e.g. cat dander).

          -  Perennial asthma requiring regular inhaled corticosteroids.

          -  Seasonal symptoms outside or during the grass-pollen season.

          -  History of emergency visit or hospital admission for asthma in the previous 12 months.

          -  History of chronic obstructive pulmonary disease.

          -  History of significant recurrent acute sinusitis.

          -  History of chronic sinusitis.

          -  At screening visit, current symptoms of upper respiratory tract infection.
             Participants may be re-evaluated for eligibility after symptoms resolve.

          -  Current smokers or a history of ≥ 5 pack years.

          -  History of life-threatening anaphylaxis or angioedema.

          -  Ongoing systemic immunosuppressive treatment.

          -  The use of any investigational drug within 30 days of the screening visit.

          -  The presence of any medical condition that the investigator deems incompatible with
             participation in the study.