Allergoids are modified allergens with an altered protein structure which are aimed at reducing allergenicity while maintaining immunogenicity and thus efficacy of allergen immunotherapy. Unlike conventional allergoids, carbamylated monomeric allergoids act through carbamylation of the lysine group which results in higher safety than conventional products. This multicenter prospective, double-blind, randomized, placebo-controlled, phase III study, was aimed at evaluating the efficacy of tablet-based monomeric allergoid of grass compared to placebo in patients with grass pollen-induced allergic rhinoconjunctivitis (AR) with or without mild asthma.

The study included patients (12-64 years) selected with a main history of moderate/severe AR due to grass, positive skin, serum and nasal provocation tests, to be randomized in two groups: one treatment group with a single dosage of the allergoid (1,000 AU) and a second treatment group receiving sublingual placebo preparation based on a once-a-day administration without any titration. Efficacy was assessed through Combined Symptoms-Medication Score of six rhinoconjunctivitis symptoms and rescue medication use during consecutive days of grass peak (>50 grains/m3) and three months of the 2020 grass season (>3 grains/m3). Safety was monitored through the description of the treatment-related adverse events (AEs) and laboratory data.

94 randomized subjects (mean age 29.6) received 7-9 months of treatment pre-coseasonally. In the ITT population the CSMS values, in both its components, were significantly lower in the treatment group compared to placebo during the days of pollen peak (-46%; p<0.0001) and the 3 months of grass season (-30%: p< 0.0001). The frequency of treatment-related AEs was in a similar proportion in the active (71) and placebo (73) groups. No severe local reactions occurred. No treatment-related SAEs were reported in any patient and no use of epinephrine was necessary.

This trial indicates Grass allergoid tablet is associated to a clinically relevant significant improvement in AR symptoms and use of antiallergic medications, consistent during the grass peak and season, with low incidence of mild adverse reactions.