Safety of a SQ‐standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo‐controlled trial

Background: Sublingual treatment of grass pollen induced rhinoconjunctivitis might provide easier access to specific immunotherapy (SIT) and minimize the risk of serious adverse events (AEs) compared to subcutaneous SIT. Aim of the study: To identify a safe dose range for once‐daily administration of a grass allergen tablet in participants with grass pollen induced seasonal rhinoconjunctivitis. Methods: A randomized, double blind, placebo‐controlled Phase I trial was conducted outside the grass pollen season. Seven dosage groups [25 000, 75 000, 150 000, 300 000, 500 000, 750 000, or 1 000 000 standardized quality tablet (SQ‐T)], consisting of 12 participants randomized either to active treatment or placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at intervals of approximately 1 week to allow for intermittent safety reviews. Results: The grass allergen tablet did not cause any serious, systemic or significant (leading to withdrawal) AEs. The overall incidence of AEs was 74% (1013 events); all of mild or moderate intensity and most considered treatment‐related. The most frequently reported treatment‐related AEs, including irritation of the throat, and itching sensations in the mouth and ears, increased with dose. These were primarily mild in intensity, started shortly after medication intake and lasted for minutes to a few hours maximum. Objective oral findings were also dose‐dependent. No clinically significant observations were found in safety laboratory, vital signs and 12‐lead ECG. Conclusions: A sublingual grass allergen tablet in doses up to 1 000 000 SQ‐T daily caused no serious or systemic AEs displaying a safety profile that allows further investigation as once‐daily self‐medication.