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Background: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan‐conjugated birch pollen allergoids for the short‐course treatment of birch pollen–induced allergic rhinoconjunctivitis. Methods: For this prospective, randomized, double‐blind, placebo‐controlled, dose‐finding study, 246 birch pollen–allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan‐conjugated birch pollen allergoids at five pre‐seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti‐allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. Results: The highest dose of mannan‐conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose‐dependent manner (3.6‐ and 4.5‐fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to −70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). Conclusion: All doses of mannan‐conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Subcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis.In this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.During the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (p < 0.001) and 56.3% (p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group (p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001).No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe. [ABSTRACT FROM AUTHOR]