Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis
Open accessAbstract
Background The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant receptor homologous molecule on T(H)2 cells (CRTH2).Objective We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 μg once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR.Methods In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours. The primary efficacy variable was the total nasal symptom score assessed as the area under the curve (AUC)(0-6h).Results In total, 146 patients (63.7% male; mean age, 36.1 years) were randomized. The adjusted mean total nasal symptom score AUC(0-6h) was significantly reduced versus placebo with 200 mg of BI 671800 (absolute difference, -0.85; percentage difference, -17%; P = .0026), montelukast (absolute difference, -0.74; percentage difference, -15%; P = .0115), and fluticasone propionate (absolute difference, -1.64; percentage difference, -33%; P < .0001). Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P < .05 for all doses), significantly inhibited nasal inflammatory cytokine levels (IL-4 and eotaxin, P < .05; 200 mg twice daily), and induced a dose-related reduction in ex vivo prostaglandin D2-mediated eosinophil shape change.Conclusion Two hundred milligrams of BI 671800 twice daily demonstrated efficacy in treating SAR symptoms induced by environmental challenge chamber allergen exposure and had a favorable safety profile.
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Allergen challenge chambers have been intensively used in phase II clinical drug development to study dose-finding, onset of action, and duration of action.
“With the given level of technical and clinical validation, ACCs have been intensively used in clinical drug development to study pharmacological properties of new drugs during phase II trials, such as dose-finding,1039-1041 onset of action,1042-1046 and duration of action.1047-1049”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1039]
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International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
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- Authors
- Krug, N., Gupta, A., Badorrek, P., Koenen, R., Mueller, M., Pivovarova, A., Hilbert, J., Wetzel, K., Hohlfeld, J. M., & Wood, C.
- Affiliations
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (United States) (US)
- Corresponding author
- Krug, Norbert
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 133
- Issue
- 2
- Pages
- 414-419.e8
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2025228731
- Cited by
- 57
- References
- 27
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 12 · 2015: 5 · 2014: 4
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Boehringer Ingelheim
- AstraZeneca
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- allergic rhinitis, CRTH2 antagonist, prostaglandin D2 receptor, montelukast, fluticasone propionate, nasal symptoms, eosinophils, IL-4, eotaxin, nasal inflammation
- MeSH terms
- Adult, Allergens, Benzamides, Double-Blind Method, Eosinophils, Female, Poaceae, Rhinitis, Allergic, Seasonal, Humans, Leukocyte Count, Male, Middle Aged, Nasal Mucosa, Pollen, Pyrimidines, Receptors, Immunologic, Receptors, Prostaglandin, Cytokines, Treatment Outcome, Cross-Over Studies, Anti-Allergic Agents
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