Evaluation of Optimal Dosing of Beltavac with Polymerized Grass Pollen Extract in Allergic Rhinoconjunctivitis with or without Asthma

The primary objective of this randomized, double-blind, placebo-controlled clinical trial is to establish the optimal therapeutic dose of **Beltavac®**, a polymerized extract of grass pollen mixture, administered in a rush regimen for the treatment of **allergic rhinoconjunctivitis**. This objective is clinically relevant as determining the optimal dose can enhance treatment efficacy and safety for patients suffering from allergic rhinoconjunctivitis, potentially improving their quality of life and reducing the burden of symptoms.

Secondary objectives include assessing the impact of the treatment on allergic rhinoconjunctivitis symptoms and medication intake during the pollen season. These evaluations are crucial for understanding the broader effects of the treatment on patient well-being and daily functioning, as well as its potential to reduce reliance on additional medications.

The clinical trial involves participants diagnosed with **allergic rhinoconjunctivitis** due to exposure to grass pollen. The study population includes both male and female subjects, aged between 18 and 65 years, who are in good physical and mental health. Participants are required to have normal renal and liver function, with any deviations being non-clinically significant. The trial does not involve a vulnerable population. Participants were selected based on their medical history of allergic rhinoconjunctivitis and moderate to severe rhinitis for at least the previous two pollen seasons, as well as a confirmed diagnosis of controlled asthma, if applicable. They must also have a positive skin prick test and specific IgE against grass pollen allergens. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the willingness and ability to complete a PROGRASS Diary Patient App during the pollen season. Key inclusion criteria involve a negative pregnancy test for females of childbearing potential and the use of effective contraception methods. The trial aims to establish the optimal therapeutic dose of Beltavac® for treating allergic rhinoconjunctivitis.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the optimal dose of Beltavac® with a polymerized extract of grass pollen mixture in patients with **allergic rhinoconjunctivitis** associated or not with asthma. The trial will span approximately 24 months, with an estimated recruitment start date of August 1, 2024, and an estimated end date of August 30, 2025. Participants will be randomly assigned to receive either the active treatment or a placebo, both administered via subcutaneous injection. The primary objective is to establish the optimal therapeutic dose of Beltavac® for the treatment of allergic rhinoconjunctivitis.

The sequence of study visits includes an initial screening visit, where eligibility criteria such as age, health status, and confirmed diagnosis of grass pollen allergy will be assessed. Participants must provide informed consent and meet specific inclusion criteria, including a negative pregnancy test for females of childbearing potential. Following the screening, eligible participants will undergo randomization and begin the treatment phase. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The primary endpoint is the proportion of patients whose reactivity to the Conjunctival Provocation Test (CPT) with grass extract decreases between baseline and visit 7. Secondary endpoints include combined nasal and conjunctival symptoms and rescue medication scores obtained during the peak pollen season.

The expected length of participant involvement is up to 24 months, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The study will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the trial.

The clinical trial involves the administration of **BELTAVAC polymerized grass mix**, which is a **suspension for injection**. This experimental medication contains an **allergenic extract of grass pollen mixture** from Dactylis glomerata, Festuca pratensis, Lolium perenne, Phleum pratense, and Poa pratensis in equal parts, polymerized to enhance its therapeutic efficacy. The pharmaceutical form is a suspension for injection, and it is administered via **subcutaneous injection**. The maximum daily dose is 0.5 ml, with a total maximum dose of 0.5 ml over a treatment period of 24 weeks. The product is not a pediatric formulation and is used as part of an **immunotherapy** regimen. Participant compliance is monitored through regular dosing schedules and follow-up visits.

The trial also includes a **placebo** group, where participants receive a **solution for injection** that is chemically inert. The placebo is administered via **subcutaneous injection** as well, with a maximum treatment period of 24 weeks. The placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators know which treatment is being administered, thus eliminating bias in the assessment of the experimental medication's efficacy.

Additionally, the study employs **conjunctival provocation and Beltapricks-tests** as auxiliary procedures to assess allergic responses. These tests are categorized under **tests for allergic diseases** and are used locally. The maximum daily dose for these tests is 5 AU/ml, with a total maximum dose of 5 AU/ml over a treatment period of 3 weeks. These tests are integral to the study as they provide objective measures of the participants' allergic reactions, complementing the subjective assessments of symptom relief.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the proportion of patients whose reactivity to the **Conjunctival Provocation Test (CPT)** with grass extract decreases between baseline and visit 7. This is defined as the titrated 10-fold step allergen concentration required to develop a positive response being at least one dose higher. Secondary endpoints include the combined nasal and conjunctival symptoms and rescue medication score (CSMS) obtained during the peak pollen season through the Diary patient App, as well as the nasal and conjunctival symptoms score and rhinoconjunctivitis daily medication score, both also obtained during the peak pollen season through the Diary patient App.