Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine

• immunological response to GrassMATAMPL versus GrassMATA (rye specific)
• allergenicity of the modified grass pollen allergoid using skin prick testing
• tolerability of native allergen, modified allergen and tyrosine adsorbents +/- MPL in the skin prick tests
• tolerability of the different dose steps compared between GrassMATAMPL and GrassMATA treatment groups
• the tolerability of the cumulative subcutaneous doses compared between GrassMATAMPL and GrassMATA treatment groups
• safety laboratories
• vital signs
• 12-lead electrocardiogram (ECG)
• number of adverse events
• number of adverse reactions

Allergen-specific immunotherapy (SIT), the administration of gradually increasing quantities of an allergen extract to an allergic patient, is a curative approach which directly treats the underlying allergic disease. GrassMATAMPL has been developed to provide pre-seasonal specific immunotherapy for patients with an allergy to grass and rye pollen (hay fever).

The tolerability and immunogenicity of GrassMATA (allergen modified with glutaraldehyde and adsorbed to tyrosine) with and without MPL adjuvant (monophosphoryl lipid A, extracted from a bacterial cell surface) is being investigated in this double-blind, randomized Phase IIa study in volunteers allergic to grass and rye pollen.

Additionally, this study will assess residual allergenicity of the modified grass and rye pollen in the product GrassMATAMPL using skin prick testing in volunteers allergic to grass and rye pollen.

Inclusion Criteria:

• Patients must have a positive skin prick test for grass and rye allergen
• Specific IgE for grass and rye with class >= 2
• History of at least 1 season of moderate to severe seasonal rhinoconjunctivitis due to an IgE-mediated allergy to pollen from grass and rye
• Males or non-pregnant, non-lactating females who are post-menopausal or naturally or surgically sterile. Females of childbearing potential have a confirmed absence of pregnancy according to a negative urine pregnancy test and must be using an acceptable birth control method

Exclusion Criteria:

• Acute or subacute atopic dermatitis and/or urticaria factitia and/or urticaria due to physical or chemical influence and/or chronic dermatitis
• Patient has moderate to severe asthma.
• Visual inspection of the forearms indicates potential problems with the conduct or interpretation of the skin prick test; both forearms must be available for testing
• History or presence of diabetes, cancer or any clinically significant cardiac, metabolic renal, hematologic diseases or disorders
• Recent clinically significant history (within 2 years) of hepatic gastrointestinal, dermatologic, venereal, neurologic or psychiatric diseases or disorders
• Any clinically significant (as determined by the investigator) abnormal laboratory value at Visit 0
• Perennial allergens: clinically relevant sensitivity against house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), molds (Cladosporium cladosporoides, Alternaria alternata, Penicillium chrysogenum, Aspergillus fumigatus) and epithelia (cat [Felis domesticus], dog [Canis familiaris])
• Patient has clinically relevant sensitivity against the following summer/autumn season flowering plants: Plantago lanceolata (plantain), Atriplex sp. (orache), Urtica dioica (nettle), Artemisia vulgaris (mugwort), Cynodon dactylon (Bermuda grass), or Ambrosia elatior (ragweed).
• Secondary alteration at the affected organ (i.e. emphysema, bronchiectasis)
• History of autoimmune diseases and/or rheumatoid diseases
• Patients who are taking b-blockers for any indication
• Patients who are not allowed to receive adrenalin
• Patients in whom tyrosine metabolism is disturbed
• Presence of a disease with a pathogenesis interfering with the immune response and patient has received medication which could influence the results of this study
• Documented evidence of acute or significant chronic infection
• History of anaphylaxis
• History of angioedema
• Hypersensitivity to the excipients in the study medication
• Previous or current hyposensitization therapy with comparable grass allergen extracts
• Currently using anti-allergy medication and other drugs with antihistaminic activity
• Patient is pregnant or planning pregnancy and/or lactating
• Patient has received treatment with preparation containing monophosphoryl lipid A during the past 12 months.