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.

The primary objective of this trial is to establish the efficacy and safety of sublingual immunotherapy with Dermatophagoides pteronyssinus extract in patients with moderate-to-severe allergic rhinitis and rhinoconjunctivitis due to house dust mites. The evaluation focuses on the Combined Symptom and Medication Score (CSMS) as the primary efficacy parameter, which integrates both symptomatic burden and rescue medication use. Additionally, the trial aims to assess the benefit-risk balance across different dose levels of the investigational product, which is clinically relevant for determining the optimal therapeutic dose that maximizes efficacy while maintaining an acceptable safety profile in patients with perennial allergic disease caused by house dust mite sensitization.

This clinical trial enrolled a total of **824 participants** diagnosed with **moderate-to-severe allergic rhinitis** or **rhinoconjunctivitis** due to **house dust mites** (HDM) for at least one year, as defined by the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline. The study population included both **male and female** participants aged **18 to 65 years**. Participants were selected based on confirmed sensitization to **Dermatophagoides pteronyssinus**, demonstrated through positive **skin prick testing** (wheal diameter ≥ 3 mm), serum **allergen-specific IgE** levels ≥ 0.7 kU/L, and a positive **nasal provocation test** with D. pteronyssinus allergen extract. Some participants presented with well-controlled mild-to-moderate **asthma** as defined by the Global Initiative for Asthma (GINA) guideline, while others had no asthma. For asthmatic participants, **forced expiratory volume** (FEV1) in one second was required to exceed 70% of the predicted normal value. Participants were required to demonstrate a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 based on the most severe days during the winter preceding enrollment. The trial excluded vulnerable populations. All participants were expected to demonstrate compliance and ability to complete an electronic diary for symptom and medication tracking. Safety laboratory results were required to be within normal range or not clinically significant.

This clinical trial is a prospective, international, randomized, double-blind, placebo-controlled, multicentre, phase II-III study designed to assess the efficacy and safety of sublingual immunotherapy in patients with moderate-to-severe allergic rhinitis or rhinoconjunctivitis due to house dust mites. The study evaluates three different doses of Dermatophagoides pteronyssinus extract administered as a sublingual spray solution compared to placebo. The investigational products include SLI-RX-DPT high dose, SLI-RX-DPT mid dose, and SLI-RX-DPT low dose, with each active treatment administered at a maximum daily dose of 0.2 ml via sublingual use. The placebo preparation is identical to the active products except that it does not contain the allergen extract.

The primary objective is to establish the efficacy and safety of SLI-RX-DPT in terms of Combined Symptom and Medication Score (CSMS) and to determine the benefit-risk balance between the different doses. The primary endpoint is defined as the absolute differences in mean CSMS during the Primary Efficacy Evaluation Period (PEEP) of each active treatment group compared with the placebo treatment group. Secondary endpoints include absolute and relative differences in mean daily Symptom Score (dSS) and daily Medication Score (dMS) during PEEP, changes in individual nasal symptom scores, assessment of quality of life using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), evaluation of Global Rhinoconjunctivitis Discomfort using a Visual Analogue Scale (VAS), analysis of well days, severe days, and symptom-free days, and evaluation of response to titrated Nasal Provocation Test (tNPT). Safety and tolerability are assessed by monitoring Treatment-Emergent Adverse Drug Reactions (TEADR) in each treatment group.

Eligible participants are female or male patients between 18 and 65 years of age who have experienced moderate-to-severe allergic rhinitis or rhinoconjunctivitis due to house dust mites for at least one year according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline. Patients may have well-controlled mild-to-moderate asthma as defined in the Global Initiative for Asthma (GINA) guideline or may be without asthma. Asthmatic patients must have a forced expiratory volume (FEV1) in one second greater than 70% of predicted normal value. Sensitization to Dermatophagoides pteronyssinus must be verified by positive skin prick test (wheal diameter ≥ 3 mm), serum allergen-specific IgE to D. pteronyssinus ≥ 0.7 kU/L, a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 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. Patients must demonstrate compliance and ability to understand and complete an electronic diary for self-evaluation of symptoms and rescue medication. Safety laboratory results must be within the normal range or considered not clinically significant.

The maximum treatment period for each investigational product is 312 days, with a maximum total dose of 62.4 ml administered throughout the treatment duration. The estimated recruitment start date is March 2026, and the estimated end date of the trial is March 2028. Participant involvement spans the entire treatment period of approximately 312 days, during which patients self-administer the assigned treatment daily and record symptoms and rescue medication use in an electronic diary. The study includes screening procedures with nasal provocation testing at baseline and post-treatment assessment to evaluate changes in response to allergen challenge. Conditions that may lead to early termination from the study are not specified in the available data.

This clinical trial evaluates three dose levels of experimental **sublingual immunotherapy** products containing **Dermatophagoides pteronyssinus extract** as the active substance, a structurally diverse allergen derived from **house dust mite**. The investigational medicinal products are designated as **SLI-RX-DPT high dose**, **SLI-RX-DPT mid dose**, and **SLI-RX-DPT low dose**, all manufactured by ROXALL MEDIZIN GMBH. Each formulation is presented as a **sublingual spray, solution** and is administered via the **sublingual route**. The maximum daily dose for all three dose levels is 0.2 millilitres, with a maximum total dose of 62.4 millilitres administered over a maximum treatment period of 312 days. All three experimental products are classified under ATC code V01AA03 (house dust).

The trial includes a **placebo** preparation that is identical to the active treatment in all aspects except that it does not contain the active substance, specifically the allergen extract. The placebo serves as the **comparator treatment** in this randomized, double-blind, placebo-controlled study design. The pharmaceutical form and route of administration for the placebo are designed to match those of the experimental products to maintain blinding integrity throughout the trial.

The dosing schedule involves daily administration of the assigned treatment, with each participant receiving 0.2 millilitres per day for up to 312 days. The trial employs a dose-ranging approach to establish the efficacy and safety profile of SLI-RX-DPT and to determine the optimal benefit-risk balance among the three dose levels tested. Compliance monitoring procedures are implemented to ensure adherence to the prescribed dosing regimen throughout the treatment period.

Efficacy will be assessed using the Combined Symptom and Medication Score (CSMS) as the primary endpoint, defined as the absolute differences in mean CSMS during the Primary Efficacy Evaluation Period (PEEP) of each active treatment group compared with the placebo treatment group. Secondary efficacy parameters include absolute and relative differences in mean daily symptom score (dSS) during PEEP, absolute and relative differences in mean daily medication score (dMS) during PEEP, and absolute and relative differences in the four mean nasal individual symptom scores during PEEP. Additional assessments involve changes in Global Rhinoconjunctivitis Discomfort measured with a 10.0-point Visual Analogue Scale (VAS) comparing pre-treatment (baseline) and post-treatment scaling between active and placebo groups, as well as changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) comparing baseline and post-treatment scoring.

Further efficacy measures include the evaluation of well days and severe days during the PEEP. A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS less than 0.5 on a 0-3 scale. A severe day is defined as a day with a single score of 3 in any of the four symptoms. Percentages of well and severe days will be calculated for each subject as the number of such days in the PEEP in relation to the 56 days comprising the PEEP. Symptom-free days are defined as days with absence of symptoms (dSS = 0) and without administration of any rescue medication (dMS = 0), expressed as a percentage of days during the PEEP. The titrated Nasal Provocation Test (tNPT) will be performed to assess efficacy by determining the percentage of patients with an increased dosing step and the change in the number of dosing steps needed to provoke a positive response post-treatment compared with pre-treatment in each of the four treatment groups, based on the response to nasal provocation with incremental concentrations of Dermatophagoides pteronyssinus allergen extract from baseline to post-treatment.