Phase II-III study to assess the efficacy and safety of subcutaneous cluster-immunotherapy in patients suffering from house dust mite allergy

Prior treatment

• Previous immunotherapy with allergen extract of house dust mites (HDM) according to the homologous group of the 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
• Serious systemic reactions to allergen-specific immunotherapy in the past
• Therapy with immunoglobulins
• Completed or ongoing treatment with 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
• Systemic and local (eye drops) treatment with beta-blockers
• 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 specific immunotherapy with other allergens
• Participation, meaning randomization, in a 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 D. farinae), which interfere with the conduct of the study (e. g. with the tNPT or the CSMS recording), especially if the result in SPT for this allergen is higher than that for D. pteronyssinus
• Severe acute or chronic inflammatory or infectious diseases
• Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function (any renal failure for patients in the subgroup for aluminum PK determinations)
• Contraindication for adrenalin (for example, acute or chronic symptomatic coronary heart disease, severe hypertension, hyperthyroidism, glaucoma)

Other

• Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2024)
• Asthmatic patients with FEV1 ≤ 80 % 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
• Patients with co-sensitizations to any perennial or seasonal allergen with overlapping during PMP but which are not cross-reactive with D. pteronyssinus and with specific IgE levels ≥ class 2 CAP/PHADIA
• Relationship or dependence with the sponsor and/or investigator
• 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 SCIT (Pitsios et al., 2015; Pfaar et al., 2022)
• Contraindications for SPT
• Contraindications for NPT

• Patients who signed and dated 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 / rhino-conjunctivitis due to house dust mites (HDM) for at least one year according to the Allergic Rhinitis and its Impact on Asthma (ARIA, Bousquet et al., 2008) guideline, either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2024) or without asthma
• Forced expiratory volume (FEV1) in one second > 80 % 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 Rhinitis 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