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)

Rationale: Allergic rhinitis/rhinoconjunctivitis (ARC) is a global health problem, affecting 10-25% of the population. Allergen-specific immunotherapy is the only disease-modifying therapeutic option for subjects with house dust mites (HDM)-induced allergic rhinitis/rhinoconjunctivitis. This Phase 3 clinical study aims to demonstrate the effecacy of PURETHAL Mites (PM) Mixture subcutaneous immunotherapy (SCIT) compared to a placebo over one year of treatment in patients with moderate to severe HDM- induced allergic rhinitis/rhinoconjunctivitis (ARC), while also prioritizing the safety of the treatment. PM Mixture is a suspension of chemically modified extract from the house dust mites Dermatophagoides pteronyssinus (D. pter) and Dermatophagoides farinae (D. far), adsorbed to aluminium hydroxide. Modified extracts (allergoids) are associated with reduced allergenicity but with preserved immunogenicity. Based on the previous studies the dose of 0.5 mL of PM Mixture solution with concentration 50,000 AUeq/mL (allergen units in millilitre) was selected for this Phase 3 clinical study. Objectives: The primary objective is to assess the efficacy of PM Mixture 50,000 AUeq/mL (0.5 mL) SCIT based on an average Total Combined Rhinitis Score (TCRS), which will be compared between PM Mixture and placebo groups. The TCRS consists of rhinitis symptom score and medication score measured daily over the last 8 weeks of the 1 year treatment. Other secondary efficacy parameters will be compared between treatment groups to show efficacy: rhinitis symptom and medication scores separately as well as a combined symptom and medication score for nasal symptoms only (CSMS(n)); Total Combined Conductivities Score; nasal provocation test; immunological blood markers such as immunoglobulins E, G and G4; and Rhinitis Quality of Life Questionnaire (standardised) (RQLQ(S)). Trial design: This is a randomized, double-blind, placebo controlled multi-centre clinical trial where subjects are participating for about 14 months. Trial population: Patients (18-65 years of age) suffering from moderate to severe ARC induced by HDM with or without controlled asthma can be included in the study. The main criteria to evaluate the HDM allergy will be done by the following parameters: allergic medical history to HDM minimum 1 year; positive skin prick test and nasal provocation test HDM D. pter and/or D. far; certain level of allergen-specific immunoglobulin E to D. pter or D. far, and most importantly they should have sufficient rhinitis symptom score measured during 2 weeks at screening. Additionally patients should have sufficient lung functions confirmed by the spirometry, they may have asthma which should be controlled. Patients with a chronic or acute disease that might place the subject at an additional risk will not be included. Certain medications which can interfere with the study treatment or increase the health risks should be washed-out and can not be taken during the study. Approximately 920 HDM-allergic subjects will be screened in order after the screening period to enroll 552 subjects.