Grass Pollen Immunotherapy Using a Cluster Regime for Seasonal Rhinitis and Asthma

Inclusion Criteria:

• Male and female 18-60 years of age
• Written informed consent obtained before entering the trial
• A clinical history of grass pollen induced allergic rhinoconjunctivitis of two yearsor more requiring treatment during the grass pollen season
• A clinical history of severe rhinoconjunctivitis symptoms (interfering with usualdaily activities or sleep), which remain troublesome despite treatment withanti-allergic drugs during the grass pollen season
• Positive Skin Prick Test (SPT) response (wheal diameter ≥ 5 mm) to Phleum pratense
• Positive specific IgE against Phleum pratense (≥ IgE Class 2)
• Physical examination with no clinically relevant findings
• If pre-menopausal female of childbearing potential, the subject must test negative onstandard urine pregnancy test and must be willing to practice appropriatecontraceptive methods for the duration of the trial
• Patients with seasonal asthma only if their baseline methacholine PC20 was greaterthan 2 mg/mL (normal range > 16 mg/ mL)
• Willingness to comply with this protocol

Exclusion Criteria:

• FEV1 < 70% of predicted value
• A clinical history of symptomatic seasonal allergic rhinitis and/or asthma due to treepollen or weed pollen adjacent to the start of - and potentially overlapping - thegrass pollen season
• A clinical history of significant symptomatic perennial allergic rhinitis and/orasthma caused by an allergen to which the subject is regularly exposed
• A clinical history of significant recurrent acute sinusitis (defined as 2 episodes peryear for the last two years all of which required antibiotic treatment) or chronicsinusitis
• At randomisation, current symptoms of, or treatment for, upper respiratory tractinfection, acute sinusitis, acute otitis media or other relevant infectious process (serous otitis media is not an exclusion criterion)
• History of emergency visit or admission for asthma in the previous 12 months
• Use of an investigational drug within 30 days prior to screening
• Previous treatment by immunotherapy with grass pollen allergen or any other allergenwithin the previous 5 years
• History of anaphylaxis, including anaphylactic food allergy, bee venom anaphylaxis,exercise anaphylaxis or drug induced anaphylaxis
• History of angioedema
• Any of the following underlying conditions known or suspected to be present:
• Cystic fibrosis
• Malignancy
• Insulin-dependent diabetes
• Malabsorption or malnutrition
• Renal or hepatic insufficiency
• Chronic infection
• Drug dependency or alcoholism
• Ischemic heart disease or angina requiring current daily medication or with anyevidence of disease making implementation of the protocol or interpretation ofthe protocol results difficult or jeopardising the safety of the subject (e.g.clinically significant cardiovascular, serious immunopathologic, immunodeficiencywhether acquired or not, hepatic, neurologic, psychiatric, endocrine, or othermajor systemic disease)
• Immunosuppressive treatment
• History of hypersensitivity to the excipients of the trial medications
• History of allergy, hypersensitivity or intolerance to trial medications or rescuemedications
• A mental condition rendering the subject unable to understand the nature, scope andpossible consequences of the trial, and/or evidence of an uncooperative attitude
• Unlikely to be able to complete the trial, for any reason, or likely to travel forextended periods of time during the grass pollen season