Efficacy and Safety Evaluation of Subcutaneous Cluster-Immunotherapy with Dermatophagoides Pteronyssinus Allergoid in Moderate-to-Severe House Dust Mite Allergy

The primary objective of this Phase II-III study is to determine the most effective and best-tolerated dose of **CLU-RX-DPT** in patients with moderate-to-severe allergic rhinitis or rhino-conjunctivitis due to house dust mites. The evaluation focuses on the benefit-risk balance and the Combined Symptom and Medication Score (CSMS). This is clinically relevant as it aims to optimize treatment efficacy while minimizing adverse effects, thereby improving patient outcomes in managing allergic conditions associated with house dust mites.

The clinical trial involves a total of **772 participants** who are both male and female, aged between **18 and 65 years**. The study population consists of individuals diagnosed with **moderate-to-severe allergic rhinitis** or rhino-conjunctivitis due to house dust mites, as per the "Allergic Rhinitis and its Impact on Asthma" guideline. Participants may have well-controlled mild-to-moderate asthma or no asthma at all. The selection criteria required participants to have a forced expiratory volume in one second greater than 80% of the predicted normal value for asthmatic patients. Sensitization to Dermatophagoides pteronyssinus was verified through a positive skin prick test and serum allergen-specific IgE levels. Participants were required to demonstrate compliance and the ability to use an electronic diary for self-evaluation of symptoms and medication use. The trial does not include a vulnerable population, and safety laboratory results were required to be within normal ranges or not clinically significant. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy and safety of subcutaneous cluster-immunotherapy in patients with moderate-to-severe **allergic rhinitis** or rhino-conjunctivitis due to house dust mites. This is a Phase II-III, randomized, double-blind, placebo-controlled study. The trial aims to determine the most effective and best-tolerated dose of CLU-RX-DPT, a solution for injection containing **Dermatophagoides pteronyssinus allergoid**, glutaraldehyde-modified. The study will compare three different doses of CLU-RX-DPT (low, mid, and high) against a placebo, which is identical in appearance, smell, taste, and excipients but lacks the active substance.

The trial is expected to commence recruitment on May 1, 2025, and conclude by April 15, 2027. Participants will be involved in the study for a maximum treatment period of 48 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age, diagnosis, and sensitization to **Dermatophagoides pteronyssinus**; regular follow-up visits to monitor safety and efficacy; and an end-of-study visit to assess the final outcomes. The primary endpoint is the absolute difference in mean Combined Symptom and Medication Score (CSMS) during the peak mite period (PMP) between each active treatment group and the placebo group. Secondary endpoints include differences in daily symptom scores (dSS), daily medication scores (dMS), and quality of life assessments.

Participants are expected to comply with study procedures, including the use of an electronic diary for self-evaluation of symptoms and medication use. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent prior to any study-specific procedures.

The clinical trial involves the administration of several treatments to evaluate the efficacy and safety of subcutaneous cluster-immunotherapy in patients with house dust mite allergy. The experimental medication, **CLU-RX-DPT**, is available in three dosage forms: low dose, mid dose, and high dose. Each formulation is a **solution for injection** containing the active substance **Dermatophagoides pteronyssinus allergoid, glutaraldehyde-modified**. This active substance is a structurally diverse allergen modified with glutaraldehyde. The pharmaceutical form for all doses is a solution for injection, and the route of administration is transdermal use. The maximum daily dose is 0.7 ml, with a total maximum dose of 5.2 ml over a treatment period of 48 weeks. The product is manufactured by ROXALL MEDIZIN GMBH and is not a pediatric formulation.

The trial also includes a **placebo** preparation for subcutaneous use. This placebo is designed to mimic the appearance, smell, taste, and excipients of the verum but does not contain the active substance, i.e., the allergen extract. The placebo serves as a comparator treatment to assess the efficacy of the experimental medication. The placebo is administered in the same manner as the experimental treatments to ensure consistency in the trial protocol.

The efficacy of the clinical trial will be assessed using the **Combined Symptom and Medication Score (CSMS)** as the primary endpoint. This endpoint will measure the absolute differences in mean CSMS during the peak mite period (PMP) for each active treatment group compared to the placebo group. Secondary endpoints include absolute and relative differences in mean daily Symptom Score (dSS) and daily Medication Score (dMS) during PMP, as well as the Global Rhinoconjunctivitis Discomfort assessed with a 10-point Visual Analogue Scale (VAS). Additionally, changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores between active and placebo groups will be evaluated, comparing baseline and post-treatment scores.

Further secondary endpoints involve the calculation of percentages of well and severe days, defined by specific criteria related to symptom scores and medication use, over a 56-day period comprising the PMP. Symptom-free days, characterized by the absence of symptoms and rescue medication, will also be expressed as a percentage of days during PMP. The trial will assess the efficacy of each dose of CLU-RX-DPT compared to placebo through the titrated Nasal Provocation Test (tNPT), which evaluates the percentage of patients with an increased dosing step and changes in the number of dosing steps needed to provoke a positive response post-treatment compared to pre-treatment.