Twin SUBLIVAC® Grasses Clinical Efficacy Study

• CIS derived variables [ Time Frame: June, July and August 2007 ] [ Designated as safety issue: No ]
• RQLQ, quantitative skin prick test [ Time Frame: Pollen season 2006 and 2007 ] [ Designated as safety issue: No ]
• oral allergy syndrome [ Time Frame: October 2006 until September 2007 ] [ Designated as safety issue: No ]
• mast-cell serum tryptase [ Time Frame: 6 months therapy ] [ Designated as safety issue: No ]
• specific immunoglobulins (IgE and IgG). [ Time Frame: 6 months therapy ] [ Designated as safety issue: No ]

• CIS derived variables
• RQLQ, quantitative skin prick test
• oral allergy syndrome
• mast-cell serum tryptase
• specific immunoglobulins (IgE and IgG).

To show that treatment with SUBLIVAC® Grasses is clinically effective by means of reduction in allergic symptoms and/or use of allergic symptomatic medication in subjects suffering from IgE mediated allergic complaints triggered by grass pollen.

Indication under study: IgE mediated allergic disorders triggered by grass pollen.

Number of centres: approximately 50.

Study period planned: Q2-2006 until Q3-2008 Analysis after one exposed season (2007); based on the outcome the study will be stopped or continued for another season.

Subject selection criteria: Seasonal rhinitis and/or rhinoconjunctivitis with or without mild asthma (FEV1 > 70%) related to grass pollen, age 12 years or older.

Dosage schedule: Start with two drops daily of SUBLIVAC® and increase by two drops daily, until the maintenance dose of 10 drops SUBLIVAC® GrassesSUBLIVAC® Grasses is reached.

Route of administration: Sublingual application (drops are to be held underneath the tongue for 2-3 minutes and then will be swallowed).

Duration of treatment: 6 to 12 months blinded per subject . Efficacy parameters

• Rhinitis, Allergic, Seasonal
• Conjunctivitis, Allergic

• Drug: SUBLIVAC® Grasses/Placebo treatment
  SUBLIVAC® Grasses/Placebo treatment
• Drug: SUBLIVAC® Grasses treatment
  SUBLIVAC® Grasses treatment
• Drug: Placebo treatment
  Placebo treatment

• Active Comparator: 1
  SUBLIVAC® Grasses treatment
  Interventions:

  • Drug: SUBLIVAC® Grasses/Placebo treatment
  • Drug: SUBLIVAC® Grasses treatment
• Placebo Comparator: 2
  Placebo treatment
  Interventions:

  • Drug: SUBLIVAC® Grasses/Placebo treatment
  • Drug: Placebo treatment

Inclusion Criteria:

• Subjects with allergic rhinoconjunctivitis with or without mild asthma FEV1 ≥ 70%) for at least 2 years. Their allergic symptoms should be related to grass pollen Use of anti-allergy symptomatic medication in the last pollen season (or, in case of a low pollen season, in one of the two previous years)
• A positive skin prick test (>3 mm) for early flowering treesgrasses and specific serum IgE-test(>1 U/ml) for grass pollen (Lolium perenne, Phleum pratense and Poa pratensis).

Exclusion Criteria:

• A positive SPT for perennial allergens of house dust mite
• Allergy to any of the excipients
• Symptoms related to concomitant sensitisation to perennial allergens of pets
• Chronic asthma or emphysema, particularly with a FEV1 < 70 % of predicted value or use of inhalation corticosteroids outside grass and tree pollen season for more than two episodes and/or longer than fourteen days
• Use of symptomatic medication for more than three episodes and/or longer than three days outside the tree- or grass pollen season
• Serious immuno-pathological diseases or malignancies (including auto-immune diseases, tuberculosis, HIV)
• Inflammation and infection of the target organ
• Severe atopic dermatitis requiring systemic immuno-suppressive medication
• Allergen specific immuno-therapy treatment within the last 5 years for a period longer than three months
• History of life threatening anaphylactic events, including anaphylactic food allergy, insect venom anaphylaxis, exercise or drug induced anaphylaxis
• A positive pregnancy test, lactation or inadequate contraceptive measures Alcohol- or drug abuse
• Lack of co-operation or severe psychological disorders