Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from grass pollen allergy

Prior treatment

• Previous immunotherapy with grass pollen allergen extracts according to the homologous group of grass pollen of the "Poaceae group", as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831), within the last 5 years
• Serious systemic reactions to allergen-specific immunotherapy in the past
• Therapy with immunoglobulins
• Completed or ongoing treatment with an anti-IgE-antibody (like Omalizumab) and/or checkpoint-inhibitor
• Malignancy within the previous 5 years
• Alcohol, drug, or medication abuse within the past year and/or during the study
• Use of non-allowed medication
• Severe psychiatric, psychological, or neurological disorders; completed or ongoing longterm treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)
• Simultaneous specific immunotherapy with other allergens
• Participation in a clinical trial in the last three months before enrolment

Other illness

• Hypersensitivity to excipients of the IMP
• Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD
• Chronic or severe acute diseases of nose or eyes
• Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis)
• Diseases of the immune system including autoimmune and immune deficiencies (with exception to well-controlled Hashimoto thyroiditis and type-1 diabetes mellitus)
• Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with exception of any other Poaceae), which interfere with the conduct of the study (e. g. with the tNPT), especially if the result in SPT for this allergen is higher than that for Phleum pratense
• Severe acute or chronic inflammatory or infectious diseases
• Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function

Other

• Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2022)
• Asthmatic patients with FEV1 ≤ 70 % of predicted normal value at screening
• Active chronic urticaria
• Active severe atopic eczema
• Existing or intended pregnancy, lactation or inadequate contraceptive measures for woman with childbearing potential or a positive pregnancy test at screening
• Relationship or dependence with the sponsor and/or investigator
• Patients with co-sensitizations to any mould or pollen with overlapping season but which are not cross-reactive with Phleum pratense and with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)
• Legal incapacity
• Patients who are jurisdictional or governmentally institutionalized
• Risk of non-compliance by the patient with the study procedures
• Simultaneous participation in other clinical trials
• Contraindications for SLIT (Pitsios et al., 2015)
• Contraindications for SPT
• Contraindications for NPT

• Patients who signed and dated the informed consent form obtained prior to any study specific examination
• Female or male patients between 18 and 65 years of age at the time of signing the informed consent form
• Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to grass pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2022) or without asthma
• Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients)
• Sensitization to Phleum pratense pollen, verified by: 1. positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and 2. serum allergen-specific IgE to Phleum pratense ≥ 0.7 kU/L (CAP EAST class ≥ 2) and 3. a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during one of the two GPS preceding enrolment and 4. positive response to nasal provocation with Phleum pratense pollen allergen extract (at least at the third concentration step)
• Assumed compliance and ability of the patient to understand the patient´s electronic diary and to follow the instructions of the study staff
• Compliance and ability of the patient to complete an electronic diary for self-evaluation of the symptoms and rescue medication
• Safety laboratory results within the normal range or considered to be not clinically significant in any other case