Specific immunotherapy for IgE mediated sensitization to birch pollen. Long-term study to assess safety and efficacy of Depigoid(R)Birch 5000 - a modified pollen extract of Betula alba (Birch) - versus placebo.

Investigation of the long-term efficacy and safety of Depigoid Birch 5000 according to the perennial treatment regimen in comparison to placebo in adult and adolescent patients with birch pollen-induced allergic rhinitis and/or rhinoconjunctivitis to show superiority vs. placebo.

As the study includes adolescent patients it is run under an approved PIP.

Total study duration per patient will be 5 years: 3 years of perennial treatment (application of study medication at intervals of 4-6 weeks) followed by a treatment-free observational phase of 2 years (seasons).

Inclusion Criteria:

• Availability of an appropriately signed and dated informed consent before any study specific examination,

• Clinical history of at least 2 years of seasonal allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma due to birch pollen allergy that has required repeated use of symptomatic treatment,

• Patients must have a minimum level of perception of symptoms from previous seasons defined as at least a moderate symptom level (i.e. a score of 2 on the 4-point-Likert scale) in at least 2 symptom categories prior to randomization,

• Lung function ≥ 80% of the predicted normal value,

• IgE-mediated sensitization has to be verified by:

  • suggestive medical history, and
  • specific IgE reactivity to birch pollen (CAP-RAST ≥ 2), and
  • a positive SPT to birch pollen at screening or within 1 months prior to the screening visit. An SPT is considered positive if it results in a wheal diameter of at least 3.0 mm

• Internet access so that patients can complete the eDiary daily via internet during all 5 pollen seasons covered by the study protocol.

Exclusion Criteria:

• History of significant clinical manifestations of allergy as a result of sensitization against co-allergies, particularly-but not limited to-grass or weed pollen and perennial allergens (e.g. house dust mites, cat or dog).
• History of anaphylactic reaction.
• Moderate or severe persistent asthma (GINA 3 or 4).
• Mild persistent asthma (GINA 2), according to the Global Initiative for Asthma Guidelines, necessitating treatment with inhaled glucocorticoids at a daily dose level of > 400 µg budesonide dose equivalents.
• Lung function < 80% of the predicted normal value (for PEF: highest result of 3 measurements).
• Acute or chronic inflammatory or infectious airway diseases including recurrent acute or chronic sinusitis.
• Chronic structural diseases of the affected organs (e.g. eye, nose, lung).
• History or presence of confirmed or potential diseases of the immune system including autoimmune diseases and immune deficiencies of actual clinical relevance.
• Any disease that prohibits the use of adrenaline (e.g. hyperthyroidism).
• Atopic dermatitis with SCORAD >30 in the past or at screening.
• Ongoing or past full courses of SIT against birch pollen within the last 5 years.
• Topical and systemic treatment with β-blockers.
• Concomitant treatment with substances interfering with the immune system beginning 1 week prior to start of treatment.
• Use of systemic corticosteroids within 3 months prior to Visit 1-1.
• Immunization with vaccines within 7 days prior to Visit 1-1.
• Treatment with antihistamines for any reason other than allergic symptoms due to birch pollen allergy.
• Changed residence between geographical regions since the last birch pollen season or not staying in the geographical region during the pre-determined birch pollen season.
• Nursing (lactating) women or women with a positive pregnancy test at the screening visit. Women of childbearing potential must be using highly effective contraception during participation in this clinical study. A highly effective method of birth control is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomised partner.