A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study to Assess the Efficacy of PURETHAL Mites Mixture 50,000 AUeq/mL Subcutaneous Immunotherapy in Adult Subjects With Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma Induced by House Dust Mite (HDM)

Exclusion Criteria

• •1. A clinically relevant history of symptomatic seasonal ARC and/or a positive SPT (mean wheal diameter ≥ 3 mm) caused by an allergen (including animal hair and dander), to which the subject is regularly exposed and/or exposure is overlapping with the e-Diary completion periods at Screening and at the end of treatment.
• •2. Nasal surgery and/or severe nasal or severe oral disease within 6 months prior to Screening.
• •3. Patients not adhering to the e-Diary procedure and/or procedure for Rescue Medication use during e-Diary phase.
• •4. Severe asthma (GINA 2022 treatment steps 4 - 5).
• •5. Uncontrolled asthma, as defined by any of the following:
• •1. Asthma Control Test (ACT) ≤19,
• •2. FEV1 ≤70% of predicted value,
• •3. Emergency room visit for asthma attack/exacerbation within 6 months prior to screening,
• •4. At least 1 hospitalization due to asthma within the last year,
• •5. History of intubation/mechanical ventilation due to asthma,
• •6. More than 2 courses of oral steroids used for treatment of asthma within the last 6 months prior to Screening,
• •7. Daily use of inhaled corticosteroids \>400mcg budesonide or equivalent.
• •6. History of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction).
• •7. Previous treatment with AIT with HDM allergen or a cross-reacting allergen for more than 1 month at the maintenance level within the last 5 years. Initiation of HDM SCIT is acceptable, if treatment has been discontinued before reaching maintenance dose.
• •8. AIT (subcutaneous, sublingual or oral) with other allergens than HDM within the last 3 months prior to screening or planned during the trial period.
• •9. Participation in a clinical trial within the last 3 months prior to screening (e.g.
• •new investigational drug or biological) or during the trial. 10. Any vaccination (including COVID-19) less than 1 week prior to screening, during screening and the up-dosing phase and the TCRS scoring periods. 11. Any immunosuppressive treatment or anti-IgE therapy within the last 6 months prior to the first dosing of the trial drug and during the trial 12. Any treatment with β-adrenergic blockers unless prescribed as per treatment standards to the subject if the medical benefit will prevail the risks upon investigators discretion. 13. Hypersensitivity to any of the other components of the investigational product. 14. Severe immune disorders (including autoimmune diseases) and/or diseases requiring immunosuppressive medication. 15. Active COVID-19 infection at the time of screening or 2 weeks before. 16. Active malignancies or any malignant disease in the last 5 years. 17. A chronic or acute disease that in the opinion of the investigator might place the subject at an additional risk, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, haematological disorders, severe atopic dermatitis, other relevant skin diseases (affecting SPT testing areas). 18. Diseases with a contraindication for the use of adrenaline/epinephrine (e.g.
• •hyperthyroidism, glaucoma). 19. Use of prohibited medication and/or not able to discontinue medications that are prohibited during the specified trial periods. 20. Moderate to severe nasal obstructive disease such as polyps, septum deviation. 21. Clinically significant chronic sinusitis or ocular infection. 22. Female subjects of childbearing potential who are pregnant or lactating. 23. Alcohol, drug, or medication abuse within the past year and during the trial.
• •24\. Any (expected) lack of cooperation or compliance upon the discretion of the investigator. 25. Severe psychiatric, psychological, or neurological disorders. 26. Employees of the Sponsor, CRO, clinical study site and/or who are 1st grade relatives, or partners of the investigator. 27. Known commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities 28. Expected changes in average HDM exposure during the trial (e.g. new avoidance measures, relocation and holidays or trips lasting more than 10 days during the efficacy assessment period)