Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis

• Average Rhinoconjunctivitis Total Symptom Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Rescue Medication Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Each of Six Individual Average Rhinoconjunctivitis Symptom Scores [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Combined Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Rhinoconjunctivitis Visual Analogue Scale Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Adjusted Visual Analogue Scale Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Rescue Medication Usage [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Proportion of Symptom-controlled Days [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Rhinoconjunctivitis Quality of Life Questionnaire [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Global evaluation of the efficacy by the patient [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Sensitization profile [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
  sensitization profile (mono- vs poly-sensitized) is derived from the skin prick test results
• Asthma [ Time Frame: Before, during and after each pollen season (over 2 years) ] [ Designated as safety issue: No ]
• Immunological markers specific for birch pollen [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
• Economical Evaluation [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
  Proportion of days-off due to birch pollen-induced symptoms
• Wheal diameter of the birch allergen Skin prick test [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
• Oral Provocation Test [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
  Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry
• Mucosa Local Inflammation [ Time Frame: Year 1 of treatment ] [ Designated as safety issue: No ]
  Analysis on a subset of patients
• Safety assessments [ Time Frame: ~20 months ] [ Designated as safety issue: Yes ]
  adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group
• Average adjusted Symptom score analysis by tertiles [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]

• Average Rhinoconjunctivitis Total Symptom Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Rescue Medication Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Each of Six Individual Average Rhinoconjunctivitis Symptom Scores [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Combined Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Rhinoconjunctivitis Visual Analogue Scale Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Average Adjusted Visual Analogue Scale Score [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Rescue Medication Usage [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Proportion of Symptom-controlled Days [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Rhinoconjunctivitis Quality of Life Questionnaire [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Global evaluation of the efficacy by the patient [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
• Sensitization profile [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
• Asthma [ Time Frame: Before, during and after each pollen season (over 2 years) ] [ Designated as safety issue: No ]
• Immunological markers specific for birch pollen [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
• Economical Evaluation [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
  Proportion of days-off due to birch pollen-induced symptoms
• Wheal diameter of the birch allergen Skin prick test [ Time Frame: Before and after each treatment period (over 2 years) ] [ Designated as safety issue: No ]
• Oral Provocation Test [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]
  Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry
• Mucosa Local Inflammation [ Time Frame: Year 1 of treatment ] [ Designated as safety issue: No ]
  Analysis on a subset of patients
• Safety assessments [ Time Frame: ~20 months ] [ Designated as safety issue: Yes ]
• Average adjusted Symptom score analysis by tertiles [ Time Frame: Year 2 of treatment ] [ Designated as safety issue: No ]

The purpose of this 2-year study is to assess the sustained clinical efficacy and safety of 300 IR/day of a sublingual solution of birch pollen allergen extract starting 4 months prior to the birch pollen season and continuing over the birch pollen season compared with placebo for reduction of rhinoconjunctivitis-related symptoms and anti-allergy medication usage.

• Hypersensitivity
• Allergic Rhinitis
• Allergic Conjunctivitis
• Seasonal Allergy

• Biological: Placebo
  10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years
• Biological: Birch pollen allergen extract
  Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years
  Other Name: Staloral Birch

• Placebo Comparator: Placebo
  Placebo sublingual solution
  Intervention: Biological: Placebo
• Experimental: Birch pollen allergen extract
  Sublingual Solution of Birch pollen allergen extract 300IR once daily 5 months per year and during 2 years
  Intervention: Biological: Birch pollen allergen extract

Inclusion Criteria:

• Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the previous 2 pollen seasons requiring intake of symptomatic treatment.
• Sensitization to birch pollen demonstrated by a positive Skin Prick Test to birch pollen with wheal diameter > 3 mm and birch pollen allergens specific IgE levels ≥ 0.70 kU/L.
• RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a maximum possible score of 18.
• Patients with an FEV1 (Forced Expiratory Volume at one second) ≥ 80% of the predicted value.
• Patients who are willing to comply with the protocol.
• Patients having given a signed informed consent before completing any study related procedure.

Exclusion Criteria:

• Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season due to any other allergens (except alder and hazel). This includes patients with symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and living with these animals at home or at risk of frequent contacts with these animals (family, friends etc.) during the course of the study.
• Patient who previously received desensitization treatment to birch pollen and/or another Betulaceae sp. (for example hazel or alder) within the previous 5 years.
• Patients with ongoing treatment by immunotherapy with another allergen.
• Pregnancy (positive pregnancy test), breast-feeding.
• Female patients of childbearing potential planning a pregnancy during this study or not using a medically accepted contraceptive method (hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], intrauterine device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner).
• Patients planning to move during the study or planning to leave the area during the birch pollen season for more than 1 week (7 consecutive days).
• Patients with moderate or severe persistent asthma (GINA 3 or 4).
• Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide dose-equivalents.
• Patients with any nasal or oral condition that could interfere with the efficacy or safety assessments (such as nasal polyposis or oral inflammation).
• Patients with severe immune deficiency.
• Patients with a past or current disease, which as judged by the Investigator, may affect the patient's participation in or outcome of this study.
• Any other disease or condition which would place a patient at undue risk by being included in the study (according to the Investigator's opinion).
• Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy whatever the route and/or immunosuppressive drugs.
• Patients treated with inhaled/systemic steroids (whatever the indication) within 4 weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12 weeks before Visit 1 (Screening).
• Patients under continuous corticotherapy (inhaled or systemic drugs).
• Patients following a strict low sodium diet as the study treatment contains 590 mg of sodium chloride per vial in a 10 mL solution.
• Investigators, co-Investigators, as well as their children or spouses and all study collaborators.

• Quintiles
• Aptuit Inc.
• Cenduit LLC
• PHT Corporation