Grass-pollen induced rhinoconjunctivitis (hay fever).
Conditions
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Atopic participants: 1. Adults age 18 to 65 years. 2. A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak symptoms in mid-May to mid-July. 3. A clinical history of moderate to severe rhino conjunctivitis symptoms with or without mild seasonal asthma interfering with usual daily activities or with sleep. 4. A clinical history of rhino conjunctivitis with or without mild seasonal asthma that remains troublesome despite treatment with either antihistamines or nasal corticosteroids during the grass pollen season. 5. Positive skin prick test response, defined as wheal diameter = 3 mm, to timothy grass pollen. 6. Positive specific IgE, defined as IgE immunoCAP = 0.7 ISU, against timothy grass pollen. 7. For women of childbearing age, a negative urine pregnancy test at the time of screening must be present and they should have expressed the willingness to use an effective form of contraception for the duration of involvement in the study. 8. The ability to give informed consent and comply with study procedures. 9. Nasal challenge with 5.000 BU/ml and consecutive Total nasal symptom score (TNSS) after 5 minutes = 7/12. Healthy, non-atopic participants: 1. Adults age 18 to 65 years. 2. Negative skin prick test response to timothy grass pollen and panel of aeroallergens. 3. Negative specific IgE, defined as IgE immunoCAP =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Atopic participants: 1. Previous grass pollen allergen immunotherapy. 2. Prebronchodilator FEV1 < 70% of predicted value at screening (out of grass-pollen season). 3. A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly and perennially exposed (e.g. cat dander). 4. Perennial asthma requiring regular inhaled corticosteroids. 5. Seasonal symptoms outside the grass-pollen season (e.g. March to April with sensitization to birch pollen giving a hint to symptomatic polyallergenic) 6. History of emergency visit or hospital admission for asthma in the previous 12 months. 7. History of chronic obstructive pulmonary disease. 8. History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment. 9. History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness. 10. At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve. 11. Current smokers or a history of = 5 pack years. 12. History of life-threatening anaphylaxis or angioedema. 13. Ongoing systemic immunosuppressive treatment. 14. The use of any investigational drug within 30 days of the screening visit. 15. The presence of any medical condition that the investigator deems incompatible with participation in the study. 16. History of fish allergy with positive skin test and/or positive specific IgE test to vertebrate/finned fish. Non-atopic participants: 1. Previous grass pollen allergen immunotherapy. 2. Prebronchodilator FEV1 < 70% of predicted value at screening (out of grass-pollen season). 3. A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly and perennially exposed (e.g. cat dander). 4. Perennial asthma requiring regular inhaled corticosteroids. 5. Seasonal symptoms outside or during the grass-pollen season. 6. History of emergency visit or hospital admission for asthma in the previous 12 months. 7. History of chronic obstructive pulmonary disease. 8. History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment. 9. History of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To understand the time course of clinical and immunological actions of grass pollen allergen immunotherapy tablets in the treatment of seasonal allergic rhinitis. ; Secondary Objective: We will assess a number of clinical and immunological effects of treatment at several time points during the study. Again, the main comparison will be after 12 months treatment and between active and placebo-treated participants. Furthermore, the healthy, atopic participants will serve as a control at 12 months. Assessment will include the following: 1. Measurement of the size (cross-sectional area in cm2) of local skin swelling caused by injection of purified grass pollen allergen into the skin of the forearm. 2. An average of hay fever symptoms and use of hay fever medications during the pollen season, as recorded by weekly diaries. 3. The results of immunological tests on blood, nasal fluid, nasal brushing and biopsy samples, such as the levels of ‘protective’ antibodies in blood serum. ;Primary end point(s): We will use a well-established Questionnaire (Total Nasal Symptom Score, TNSS) to record nasal symptoms during the first 60 minutes after nasal allergen challenge (purified grass pollen sprayed into the nose). Specifically, we will look at whether the response to the allergen challenge is different in participants receiving active treatment compared to those receiving dummy treatment (placebo), after 12 months of treatment. ;Timepoint(s) of evaluation of this end point: (please see above) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Cross-sectional area in cm2 of EPR and LPR skin responses to intradermal grass pollen allergen injection at 12 months in active versus placebo treated participants. 2. Mean combined symptom + medication scores over the course of the 2014 grass pollen season in active versus placebo-treated participants. 3. Serum and nasal fluid grass pollen specific IgG4 level and inhibition of B cell IgE-facilitated allergen binding in active versus placebo-treated patients versus non-atopic controls at 12 months. 4. Allergen-induced peripheral blood basophil activation in active versus placebo-treated participants versus non-atopic controls at 12 months. 5. Proportion of allergen-specific phenotypic Treg cells in peripheral blood as measured by flow cytometry in active vs placebo-treated patients versus non-atopic controls at 12 months. Exploratory endpoints will include, in active versus placebo-treated patients versus non-atopic controls at 12 months: the frequency of putative Breg cells in peripheral blood; the molecular binding profiles of IgE and IgG4 antibodies; T and B cell receptor sequencing; frequency of putative type 2 innate lymphoid cells (ILC2s). ;Timepoint(s) of evaluation of this end point: (please see above) | — |
Countries
United Kingdom
Contacts
Public ContactNabila Youssouf
Imperial College London
Outcome results
None listed