Background and Rationale IgE-mediated allergic diseases affect approximately 35% of the population in industrialized countries, with prevalence continuing to rise. Mugwort (Artemisia vulgaris) pollen is among the top ten global aeroallergens responsible for seasonal allergic rhinitis and allergic asthma. In Kazakhstan, mugwort pollen is the causative allergen in 68% of children and adolescents diagnosed with allergic rhinitis and asthma. Allergen-specific immunotherapy (ASIT) remains the only disease-modifying treatment for IgE-mediated allergy, capable of inducing long-term tolerance by shifting immune responses from Th2 toward Th1 and regulatory T-cell (Treg) profiles. Conventional subcutaneous ASIT (SCIT) requires 3-5 years of treatment with frequent injections, leading to low patient compliance. There is a clear unmet need for shorter, effective SCIT regimens.
Investigational Product PollenVax is an original subcutaneous allergen immunotherapy product developed by Kazakh National Agrarian Research University (KazNARU). It consists of recombinant major mugwort pollen allergen Art v 1 combined with the oil-in-water adjuvant Montanide ISA-51 (Seppic, France). The Montanide ISA-51 adjuvant forms a depot at the injection site, enabling sustained antigen release and prolonged immune stimulation. PollenVax is the first recombinant Art v 1 product formulated with Montanide ISA-51 for subcutaneous ASIT of mugwort pollen-induced allergic disease. It is designed for an ultra-short treatment course of four weekly subcutaneous injections, with the aim of improving patient compliance and reducing the number of required clinic visits compared to conventional SCIT regimens.
Preclinical Evidence Preclinical studies in mouse and guinea pig models of mugwort pollen sensitization demonstrated that PollenVax (recombinant Art v 1 + Montanide ISA-51) produced a superior immunological profile compared to other tested formulations. Key findings included: significant reduction of total and allergen-specific IgE; marked increase in protective IgG antibodies; shift from Th2-dominant to Th1-dominant immune response; and reduction of lung eosinophilic inflammation superior to sublingual immunotherapy (SLIT)-based approaches. Efficacy was demonstrated in both pre-seasonal and co-seasonal (during active pollen exposure) administration paradigms. Safety studies in guinea pigs, mice, and rats showed no anaphylactic reactions and no delayed-type hypersensitivity responses. Acute and subchronic toxicity studies in rats classified PollenVax in Hodge-Sterner Class 5 (practically non-toxic), with the No Observed Adverse Effect Level (NOAEL) established at the maximum tested dose of 0.4 mL per injection.
Phase I Clinical Evidence A completed Phase I randomized, double-blind, placebo-controlled study enrolled 30 adults with confirmed mugwort pollen-induced allergic rhinitis. Participants received PollenVax in the ultra-short SCIT regimen of four weekly subcutaneous injections at cumulative doses of 22 µg or 44 µg recombinant Art v 1, or placebo. Primary Phase I objectives were safety and tolerability.
Safety outcomes: No deaths, serious adverse events (SAEs), anaphylaxis, or high-grade systemic allergic reactions were observed. Adverse events were predominantly mild-to-moderate local injection site reactions (redness, induration, pruritus) that were transient and self-resolving without specific treatment.
Immunological outcomes: Phase I demonstrated marked induction of Art v 1-specific IgG4, minimal IgE induction, statistically significant reduction in skin prick test reactivity, and dose-dependent Th1/regulatory T-cell immune modulation - consistent with the expected mechanism of action of effective ASIT.
These Phase I results supported the safety profile and immunological activity of PollenVax and provided the basis for proceeding to this Phase II efficacy and safety study.
Statistical Approach The primary efficacy analysis will use Analysis of Covariance (ANCOVA) with the Combined Symptom and Medication Score (CSMS) as the dependent variable, treatment group as the fixed factor, and baseline sensitization measures (Art v 1-specific IgE, SPT wheal area, ALEX² molecular allergy test result) as covariates, applied to the Intent-to-Treat/Full Analysis Set (ITT/FAS) population. A linear mixed model (LMM) will additionally adjust for potential co-sensitization to Chenopodiaceae and Ambrosia pollen as confounders. The significance level is α = 0.05 (two-sided). The sample size of 46 participants per group (138 total) provides 80% power to detect a Minimum Clinically Important Difference (MCID) of 0.33 CSMS units (assumed SD = 0.7), with a 10% dropout allowance incorporated.
