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Clinical Trial
. 2025 Mar;80(3):817-826.
doi: 10.1111/all.16387. Epub 2024 Nov 9.

Short-course subcutaneous treatment with birch pollen allergoids greatly improves symptom and medication scores in birch allergy

Ralph Mösges  1   2 , Esther Raskopf  1 , Ludger Klimek  3 , Oliver Pfaar  4 , Stefan Zielen  5   6 , Elena Xenofontos  2 , Lea Decker  2 , Christian Neuhof  1 , Anna Rybachuk  1 , Cengizhan Acikel  1 , Hacer Sahin  1 , Silke Allekotte  1 , Sandra Del Pozo Collado  7 , José Luis Subiza  7 , Miguel Casanovas  7 , Mandy Cuevas  8
Affiliations
Clinical Trial

Short-course subcutaneous treatment with birch pollen allergoids greatly improves symptom and medication scores in birch allergy

Ralph Mösges et al. Allergy. 2025 Mar.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

Keywords: allergic rhinoconjunctivitis; birch pollen; combined symptom and medication score; mannan conjugate; polymerized allergoid.

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Conflict of interest statement

ER, EX, LD, CA, HS, CN, AR and SA have nothing to disclose; RM reports grants and personal fees from Inmunotek during the conduct of the trial; personal fees from ALK, grants from ASIT biotech, personal fees from allergopharma, personal fees from Allergy Therapeutics, grants and personal fees from Bencard, grants from Leti, grants, personal fees and non‐financial support from Lofarma, non‐financial support from Roxall, grants and personal fees from Stallergenes, grants from Optima, personal fees from Friulchem, personal fees from Hexal, personal fees from Servier, personal fees from Klosterfrau, non‐financial support from Atmos, personal fees from Bayer, non‐financial support from Bionorica, personal fees from FAES, personal fees from GSK, personal fees from MSD, personal fees from Johnson and Johnson, personal fees from Meda, personal fees and non‐financial support from Novartis, non‐financial support from Otonomy, personal fees from Stada, personal fees from UCB, non‐financial support from Ferrero, grants from Hulka, personal fees from Nuvo, grants and personal fees from Ursapharm, personal fees from Menarini, personal fees from Mundipharma, personal fees from Pohl‐Boskamp, grants from Cassella‐med GmbH & Co. KG, personal fees from Laboratoire de la Mer, personal fees from Sidroga, grants and personal fees from HAL BV, personal fees from Lek, personal fees from PRO‐AdWise, personal fees from Angelini Pharma, grants and non‐financial support from JGL, grants and personal fees from bitop, grants from Sanofi, personal fees from Menarini, outside the submitted work; MC declares honoraria for presentations from ALK‐Abelló, Allergopharma, AstraZeneca, Bencard Allergie/ Allergy Therapeutics, GalaxoSmithKline, HAL Allergy, Leti Pharma, Novartis, Roxall, Sanofi‐Aventis, Stallergenes outside the submitted work. Other non‐financial interests: Member of German Society of Allergy (AeDA) and German Society of Oto‐Rhino‐Laryngology, Head and Neck Surgery DGHNO‐KHC. Coordinating investigator of the present clinical trial; LK reports grants and personal fees from Inmunotek during the conduct of the trial; grants and personal fees from Allergopharma, grants and personal fees from Viatris, personal fees from HAL Allergie, personal fees form ALK‐Abelló, grants and personal fees from LETI Pharma, grants and personal fees from Stallergenes, grants from Quintiles, grants and personal fees from Sanofi, grants from ASIT biotech, grants bromoform, personal fees from Allergy Therapeut., grants from Astra‐Zeneca, grants and personal fees from GSK, grants from Inmunotek, personal fees from Cassella med, personal fees from Novartis, personal fees from Regeneron Pharmaceuticals, personal fees from ROXALL Medizin GmbH, outside the submitted work; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. OP reports grants for his institution during the conduct of the trial from Inmunotek S.L., Spain, and he reports grants and/or personal fees and/or travel support from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Laboratorios LETI/LETI Pharma, GlaxoSmithKline, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, Pohl‐Boskamp, John Wiley and Sons/AS, Paul‐Martini‐Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, Wort&Bild Verlag, Verlag ME, Procter&Gamble, ALTAMIRA, Meinhardt Congress GmbH, Deutsche Forschungsgemeinschaft, Thieme, Deutsche AllergieLiga e.V., AeDA, Alfried‐Krupp Krankenhaus, Red Maple Trials Inc., Königlich Dänisches Generalkonsulat, Medizinische Hochschule Hannover, ECM Expro and Conference Management, Technical University Dresden, Lilly, Japanese Society of Allergy, Forum für Medizinische Fortbildung, Dustri‐Verlag, Pneumolive, ASIT Biotech, LOFARMA, Almirall, Paul‐Ehrlich‐Institut, outside the submitted work; and he is Vice President of the EAACI and member of EAACI Excom, member of ext. board of directors DGAKI; coordinator, main‐ or co‐author of different position papers and guidelines in rhinology, allergology and allergen‐immunotherapy; he is associate editor (AE) of Allergy and Clinical Translational Allergy; SZ reports grants and personal fees from Inmunotek during the conduct of the trial; grants from Palas GmbH, grants and personal fees from Allergy Therapeutics GmbH, grants and personal fees from Böhringer Ingelheim, personal fees from Novartis GmbH, personal fees from Lofarma GmbH, personal fees from IMS HEALTH GmbH & Co. OHG, personal fees from GSK, personal fees from Stallergenes, personal fees from Engelhard Arzeneimittel, personal fees from Sanofi‐Pasteur, personal fees from AstraZeneca, personal fees from Erydel, outside the submitted work. SPC is an employee of Inmunotek, JLS and MC are shareholders of Inmunotek. All authors had full access to all the data in this trial and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Figures

FIGURE 1
FIGURE 1
Overview of the T502‐SIT‐045 trial design. Patients received pre‐seasonal subcutaneous injections of T502 or placebo (treatment phase). Clinical effects were assessed during the birch pollen season 2022 via assessment of CSMS and RQLQ. mTU/mL, mannan therapeutic units per millilitre; V1‐9, visit 1–9; FU, follow‐up; CSMS, combined symptom and medication score; RQLQ, rhinoconjunctivitis quality of life questionnaire.
FIGURE 2
FIGURE 2
CONSORT flow chart of the trial. ITT, intention to treat; PP, per protocol.
FIGURE 3
FIGURE 3
Combined symptom and medication score (CSMS) during the peak birch pollen season 2022 in the placebo and T502 treatment group. Data is presented as box plot (minimum, 25th percentile, median, 75th percentile, maximum, and including percentual differences of median values and corresponding p value) of the ITT set.
FIGURE 4
FIGURE 4
Mean RQLQ scores at V7 (before the birch pollen season) and at V8 (at the peak of the birch pollen season) in the placebo and T502 treatment group. Data is presented as mean CSMS+SD of the ITT set. RQLQ, rhinoconjunctivitis quality of life questionnaire.
FIGURE 5
FIGURE 5
(A) Bet v 1 sIgG4 levels (kU/L) and (B) Bet v 1 sIgE/sIgG4 ratio at baseline (V1) and after treatment (V7). Data is expressed as mean + SD. ***p < 0.0001 in comparison to baseline, ###p < 0.0001 in comparison to placebo.
See this image and copyright information in PMC

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