ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Results of a Phase 2b Dose Finding Study of Velsecorat, an Inhaled Non-Steroidal, Selective Glucocorticoid Receptor Modulator in Asthma (GRANIT)
Session Title
D7 - D007 ADVANCES IN ASTHMA THERAPIES
Abstract
A1202 - Results of a Phase 2b Dose Finding Study of Velsecorat, an Inhaled Non-Steroidal, Selective Glucocorticoid Receptor Modulator in Asthma (GRANIT)
Author Block: G. L. Chupp1, K. M. Beeh2, A. Jauhiainen3, S. Necander4, M. N. Brown5, U. Wählby Hamrén6, H. Forsman4, Y. Kurdyukova7, J. Steele8, C. Astbury9, I. Psallidas10; 1Yale Center for Asthma and Airway Disease, Yale School of Medicine, New Haven, CT, United States, 2Insaf–Respiratory Research Institute, Wiesbaden, Germany, 3Early Biostats & Statistical Innovation, Data Sciences and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 4Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 5Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, United States, 6Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden, 7Patient Safety Respiratory & Immunology, Chief Medical Office, R&D, AstraZeneca, Gothenburg, Sweden, 8Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 9Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, 10Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
Rationale Velsecorat (AZD7594) is an inhaled non-steroidal, selective glucocorticoid receptor modulator (SGRM) under development for asthma. Here we describe the results of a Phase 2b study in asthma (NCT03622112). Methods The primary objective was to determine the efficacy of velsecorat (change from baseline (CFB) in trough FEV1 vs placebo (PBO)). A composite endpoint of diary variables capturing clinically relevant deteriorations and severe exacerbations (CompEx) was a key secondary endpoint. This multi-center, parallel-arm, PBO-controlled, double-blind study enrolled adult patients with asthma inadequately controlled following run-in on low-dose budesonide (GINA step 3) to receive velsecorat (50, 90, 180, 360, 720µg), PBO or open-label 100µg fluticasone furoate (FF), once-daily for 12 weeks. Results 805 randomized patients received ≥1 dose and 661 completed the study (only 63% in the PBO group). Velsecorat demonstrated a dose-dependent improvement in CFB trough FEV1 vs PBO over the entire treatment period, but was not significant at week 12 (720 µg LS means difference 0.082L 95%CI -0.003-0.167). For velsecorat 360 & 720 µg vs PBO, sensitivity analysis showed significant differences in overall treatment trough FEV1 CFB Velsecorat 360 & 720 µg significantly delayed time to first CompEx event (HR 0.23&0.20) and reduced CompEx annual event rate (0.60&0.48vsPBO 2.42). Overall, velsecorat was safe and well-tolerated. Conclusions Velsecorat improved lung function and reduced time to first event and annual rate of CompEx events vs PBO. Primary endpoint results were likely influenced by the large proportion of early discontinuations on the PBO arm.
Author Block: G. L. Chupp1, K. M. Beeh2, A. Jauhiainen3, S. Necander4, M. N. Brown5, U. Wählby Hamrén6, H. Forsman4, Y. Kurdyukova7, J. Steele8, C. Astbury9, I. Psallidas10; 1Yale Center for Asthma and Airway Disease, Yale School of Medicine, New Haven, CT, United States, 2Insaf–Respiratory Research Institute, Wiesbaden, Germany, 3Early Biostats & Statistical Innovation, Data Sciences and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 4Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 5Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, United States, 6Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden, 7Patient Safety Respiratory & Immunology, Chief Medical Office, R&D, AstraZeneca, Gothenburg, Sweden, 8Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 9Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, 10Clinical Development, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
Rationale Velsecorat (AZD7594) is an inhaled non-steroidal, selective glucocorticoid receptor modulator (SGRM) under development for asthma. Here we describe the results of a Phase 2b study in asthma (NCT03622112). Methods The primary objective was to determine the efficacy of velsecorat (change from baseline (CFB) in trough FEV1 vs placebo (PBO)). A composite endpoint of diary variables capturing clinically relevant deteriorations and severe exacerbations (CompEx) was a key secondary endpoint. This multi-center, parallel-arm, PBO-controlled, double-blind study enrolled adult patients with asthma inadequately controlled following run-in on low-dose budesonide (GINA step 3) to receive velsecorat (50, 90, 180, 360, 720µg), PBO or open-label 100µg fluticasone furoate (FF), once-daily for 12 weeks. Results 805 randomized patients received ≥1 dose and 661 completed the study (only 63% in the PBO group). Velsecorat demonstrated a dose-dependent improvement in CFB trough FEV1 vs PBO over the entire treatment period, but was not significant at week 12 (720 µg LS means difference 0.082L 95%CI -0.003-0.167). For velsecorat 360 & 720 µg vs PBO, sensitivity analysis showed significant differences in overall treatment trough FEV1 CFB Velsecorat 360 & 720 µg significantly delayed time to first CompEx event (HR 0.23&0.20) and reduced CompEx annual event rate (0.60&0.48vsPBO 2.42). Overall, velsecorat was safe and well-tolerated. Conclusions Velsecorat improved lung function and reduced time to first event and annual rate of CompEx events vs PBO. Primary endpoint results were likely influenced by the large proportion of early discontinuations on the PBO arm.
