Randomized, Double‑Blind, Placebo‑Controlled Trial of Subcutaneous HDM (Dermatophagoides pteronyssinus, D. farinae) and Blomia tropicalis Extract in Allergic Rhinitis

The primary objective is to assess the efficacy of subcutaneous immunotherapy with a polymerized allergen extract containing Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis in patients diagnosed with allergic rhinitis/rhinoconjunctivitis attributable to house‑dust‑mite sensitization, thereby determining its therapeutic benefit relative to placebo.

Secondary objectives include:

• Evaluation of the treatment effect on allergic rhinoconjunctivitis caused by dust‑mite sensitization.
• Assessment of overall allergy symptom improvement.
• Measurement of rhinitis control outcomes.
• Determination of impact on patient‑reported quality of life.
• Analysis of changes in serum levels of specific immunoglobulins.

The trial enrolled male and female participants aged 12 to 65 years with a documented history of moderate to severe persistent allergic rhinitis/rhinoconjunctivitis due to house dust mite sensitization (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis) confirmed by skin prick test or serum‑specific IgE. Subjects required symptomatic disease for at least one year and a mean rhinitis symptom score ≥2 during a four‑week screening period. Inclusion criteria mandated a negative pregnancy test for women of child‑bearing potential, contraception use, and the ability to complete electronic patient records. Patients with asthma were eligible only if asthma was controlled (ACT score >19, FEV1 ≥80%) and met the GINA 2025 guidelines. The definition of rhinitis severity followed the ARIA Guidelines. Selection was based on these predefined criteria rather than random sampling. The sponsor did not provide information on the total number of participants enrolled.

The study is a multicenter, Allergic rhinitis/rhinoconjunctivitis trial employing a randomized, double-blind, placebo-controlled design to assess the efficacy and safety of subcutaneous immunotherapy with Beltavac® (0.5 ml suspension) compared with a matching placebo (0.5 ml). Participants undergo a screening visit lasting up to four weeks to confirm eligibility, followed by a baseline visit (Visit 1) where the first subcutaneous injection is administered. Subsequent injections and assessments occur at scheduled follow‑up visits, including Visit 7 (mid‑treatment) and Visit 13 (end‑of‑study), with the primary endpoint—the combined nasal symptom and medication score—collected daily in four‑week intervals prior to Visits 1 and 7 and in eight‑week intervals prior to Visit 13. Secondary efficacy measures, serologic assessments, and visual analogue scales are obtained at Visits 1, 7 and 13. The overall participant involvement spans approximately 16 weeks (screening plus a 12‑week treatment phase) with the final evaluation at the end‑of‑study visit. Early termination may occur for reasons such as clinically significant adverse events, pregnancy, non‑compliance with study procedures, or withdrawal of informed consent.

The investigational product, Beltavac, is a polymerized allergenic extract comprising equal parts of Dermatophagoides pteronyssinus, Dermatophagoides farinae (both glutaraldehyde‑modified allergoids), and Blomia tropicalis polymerized extract. It is supplied as a suspension for injection for subcutaneous administration at a dose of 0.5 ml per injection.

The control arm utilizes a matching placebo administered subcutaneously in a volume of 0.5 ml per injection.

Both study treatments are delivered according to the protocol‑specified dosing schedule, with each injection given via the subcutaneous route. Compliance with the dosing regimen is monitored through documented administration records and periodic verification of study drug accountability. The trial evaluates efficacy and safety in participants with allergic rhinitis/rhinoconjunctivitis sensitized to the specified mite allergens.

The primary efficacy assessment utilizes the Combined score of nasal symptoms and specific allergy medication (CSMR4), which patients record daily in an electronic diary. Scores are aggregated over 4‑week periods preceding visits 1 and 7 and over an 8‑week period preceding visit 13.

Secondary efficacy parameters include the Rhinitis Symptoms Score, Specific Medication Scale score, Nasal and Ocular Symptom Scale score, and the combined score of nasal, ocular, and medication symptoms (CSMR6). Additional measures are the percentage of days without symptoms or medication, a visual analogue scale completed by patient and investigator at visits 1, 7, and 13, the RCAT questionnaire at the same visits, and the mini‑RQLQ at visits 1, 7, and 13. Serum concentrations of specific IgE and IgG4 antibodies to Blomia, DPT, DF total, Der p1, Der p2, Der p23, Der f1, Der f2, and Blo t5 are quantified at visits 0, 7, and 13.

Efficacy data are collected using validated electronic patient‑reported outcome tools, standardized visual analogue scales, the RCAT and mini‑RQLQ questionnaires, and laboratory assays for immunoglobulin levels. Analyses compare the treatment and placebo arms at each scheduled visit, focusing on changes from baseline in the primary CSMR4 score and secondary endpoints.