Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial
| Autor: | Laurie A. Lee, William Powley, Diana Quint, Anne K. Ellis, Daphne Tsitoura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Adult Male medicine.medical_specialty medicine.drug_class Immunology medicine.disease_cause Placebo law.invention 03 medical and health sciences Young Adult 0302 clinical medicine Allergen Randomized controlled trial Piperidines law Internal medicine Immunology and Allergy Medicine Humans Adverse effect Administration Intranasal Aged business.industry Adenine Rhinitis Allergic Seasonal Allergens Middle Aged Rhinitis Allergic 030104 developmental biology Treatment Outcome Toll-Like Receptor 7 030220 oncology & carcinogenesis Anesthesia Pharmacodynamics Cohort Nasal administration Female Immunization Seasons Drug Monitoring business Biomarkers Follow-Up Studies |
| Zdroj: | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 47(9) |
| ISSN: | 1365-2222 |
| Popis: | Background Toll-like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development. Objective Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035. Methods This randomized, double-blind, placebo-controlled study (TL7116958) was conducted over two pollen seasons (2013–2014) and follow-up study (204509) conducted one year later. Participants with allergic rhinitis (n=42) were randomized to receive eight weekly doses of i.n. GSK2245035 (20 ng [2014 Cohort; n=14] or 80 ng [2013 Cohort; n=14]) or placebo (n=14). Adverse events (AEs), including cytokine release syndrome-AEs (CytoRS-AEs) and nasal symptoms were assessed. Nasal and serum IFN-inducible protein 10 (IP-10) were measured after doses 1 and 8, then 1 (follow-up visit [FUV] 1) and 3 (FUV2) weeks after final dose. Nasal allergen challenges (NAC) and allergic biomarkers assessment (nasal, serum) were conducted at baseline, FUV1, FUV2 and at a follow-up visit 1-year post final dose (FUV3; 2014 Cohort only). A Bayesian framework enabled probability statements for mean effect sizes. Results GSK2245035 induced CytoRS-AEs (most commonly headache, median duration 95% certainty). Both doses showed a trend in reducing Total Nasal Symptom Score 15 minutes post NAC at FUV1 and FUV2 but there was no reduction evident at FUV3. Nasal levels of selected allergic biomarkers demonstrated trends for reductions at FUV1, FUV2 and FUV3. Conclusions and clinical relevance Weekly i.n. GSK2245035 20 ng was well-tolerated and reduced allergic reactivity to nasal challenge for 3 weeks post treatment. Clinicaltrials. gov identifiers NCT01788813/NCT02446613 GSK identifiers TL7116958/204509 This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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