Evaluation of the Efficacy and Safety of Mannan-Conjugated Allergoids in Moderate-to-Severe Allergic Rhinitis/Rhinoconjunctivitis with or without Controlled Asthma

The primary objective of this clinical trial is to evaluate the **clinical efficacy** of EP-088_MM09, a mannan-conjugated allergoid, administered subcutaneously at a concentration of 3,000 mTU/mL. This evaluation is conducted in subjects aged 12 to 65 years with moderate-to-severe persistent **rhinitis/rhinoconjunctivitis**, with or without mild-to-moderate intermittent or persistent controlled asthma, who are allergic to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The clinical relevance of this objective lies in its potential to provide an effective treatment option for individuals suffering from these allergic conditions, thereby improving their quality of life and reducing the burden of symptoms.

Secondary objectives include: - Assessing the safety and clinical tolerability of EP-088_MM09. - Evaluating the clinical benefit of EP-088_MM09 on various efficacy parameters compared to placebo. - Investigating the effect of EP-088_MM09 on the immunological status of subjects compared to placebo. - Assessing the clinical effect of EP-088_MM09 on quality of life and symptom control compared to placebo. - Evaluating the effect of EP-088_MM09 on the consumption of health resources related to study pathologies.

The clinical trial involves participants aged **12 to 65 years** who are diagnosed with moderate-to-severe persistent **allergic rhinitis/rhinoconjunctivitis** with or without mild-to-moderate intermittent or persistent controlled asthma. Both **male and female** subjects are included in the study population. The trial does not involve a vulnerable population. Participants were selected based on their clinical history of inhalation allergy caused by **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**, confirmed by a positive skin prick test and specific IgE levels. The study requires participants to maintain a record of symptoms and medication consumption, indicating a level of engagement with their health management. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of a **mannan-conjugated allergoid** vaccine in patients with moderate-to-severe allergic rhinitis/rhinoconjunctivitis, with or without mild-to-moderate controlled allergic asthma. The trial will involve subjects aged 12 to 65 years who are allergic to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The study is expected to commence recruitment in April 2025 and conclude by January 2029, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a positive skin prick test and specific IgE levels. Following randomization, subjects will attend regular follow-up visits to monitor the **Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS)** and other secondary endpoints, including symptom scores and immunological parameters. The end-of-study visit will assess the overall efficacy and safety of the treatment, including adverse events and reactions at the administration site.

The expected length of participant involvement is up to 12 months, with conditions for early termination including non-compliance with the dosage regimen or the occurrence of severe adverse events. The trial aims to provide comprehensive data on the clinical efficacy of the investigational product compared to placebo, contributing valuable insights into the management of allergic rhinitis/rhinoconjunctivitis and associated asthma.

The clinical trial involves the administration of a **mannan-conjugated allergoid (polymerized) Dermatophagoides pteronyssinus and Dermatophagoides farinae parenteral vaccine**. This experimental medication is formulated as a **solution for injection**. The active substances include Dermatophagoides pteronyssinus enriched allergoid and Dermatophagoides farinae enriched allergoid, both of which are mannan-conjugated and polymerized. The vaccine is administered via the **subcutaneous route**. The dosing regimen involves a maximum daily dose of 0.5 ml, with a total maximum dose of 6 ml over a treatment period of 12 months. The primary objective is to evaluate the clinical efficacy of the vaccine at a concentration of 3,000 mTU/mL in subjects aged 12 to 65 years with moderate-to-severe persistent rhinitis/rhinoconjunctivitis, with or without mild-to-moderate intermittent or persistent controlled asthma, allergic to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.

The study also includes a **placebo** treatment, which is identical in solution and presentation to the active treatment but lacks active ingredients. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the active treatment, following the same dosing schedule and route of administration. This allows for a direct comparison of the efficacy and safety of the experimental vaccine against the placebo, providing a robust assessment of the treatment's impact on the target condition.

The clinical trial aims to assess the efficacy of a **Mannan-conjugated allergoid (polymerized) Dermatophagoides pteronyssinus and Dermatophagoides farinae parenteral vaccine** in patients with moderate-to-severe persistent rhinitis/rhinoconjunctivitis, with or without mild-to-moderate intermittent or persistent controlled asthma, allergic to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The primary endpoint for evaluating efficacy is the Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS), which will be recorded by subjects in a diary. Secondary endpoints include various symptom and medication scores such as the Rhinitis/Rhinoconjunctivitis Symptom Score (RSS), Rhinitis/Rhinoconjunctivitis Medication Score (RMS), and Asthma-Combined Symptom and Medication Score (ACSMS), among others. Additionally, immunological parameters such as Total IgE, Specific IgE and IgG4, and the Specific IgE/Total IgE ratio will be measured. Quality of life assessments will be conducted using the Asthma Quality of Life Questionnaire (AQLQ) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). The trial will also evaluate asthma control using the Asthma Control Questionnaire (ACQ-6) and employ a Visual Analogue Scale (VAS) for further assessment.