Phase II-III study to assess the efficacy and safety of sublingual immunotherapy in patients suffering from house dust mite allergy. A prospective, international, randomized, double-blind, placebo-controlled, multicentre, phase II-III trial.

Prior treatment

• Previous immunotherapy with allergen extract of house dust mites (HDM) according to the homologous group of Dermatophagoides genus, as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831/2008), within the last 5 years
• 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 long-term treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants)
• Simultaneous participation in other clinical trials or finished randomized participation within the last year before enrolment in this clinical trial, although the patient could be screened but not randomized in another clinical trial at least three months before enrolment in this clinical trial
• Simultaneous specific immunotherapy with other allergens
• Serious systemic reactions to allergen-specific immunotherapy in the past

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)
• Severe acute or chronic inflammatory or infectious diseases
• Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with exception of d. farinae), which interfere with the conduct of the study (e. g. with the tNPT or CSMS recording), especially if the result in SPT for this allergen is higher than that for D. pteronyssinus
• 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, 2025)
• 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
• Legal incapacity
• Patients with co-sensitizations to any perennial, such as moulds, or seasonal allergen overlapping with the PEEP but which are not cross-reactive with D. pteronyssinus and, measured at the same time, with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)
• Patients who are jurisdictional or governmentally institutionalized
• Risk of non-compliance by the patient with the study procedures
• 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 house dust mites (HDM) for at least one year according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline (Bousquet et al., 2008), either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2025) or without asthma
• Forced expiratory volume (FEV1) in one second > 70 % of predicted normal value (only for asthmatic patients)
• Sensitization to Dermatophagoides pteronyssinus, verified by: positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and serum allergen-specific IgE to D. pteronyssinus ≥ 0.7 kU/L (CAP EAST class ≥ 2) and a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during winter preceding enrolment and positive response to nasal provocation with D. pteronyssinus 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