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.
Search Tips:
- Use the keyword search to search by keyword or author's name.
- Filter your search results by selecting the checkboxes that apply.
- Click on "Clear" to clear the form and start a new search. .
Search results will display below the form.
Effect of Tezepelumab on Airway Inflammation in Patients with Moderate-to-Severe Uncontrolled Asthma: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study (CASCADE)
Session Title
TP10 - TP010 CLINICAL AND POPULATION-LEVEL STUDIES OF ASTHMA
Abstract
A1456 - Effect of Tezepelumab on Airway Inflammation in Patients with Moderate-to-Severe Uncontrolled Asthma: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study (CASCADE)
Author Block: S. E. Diver1, L. Khalfaoui1, C. Emson2, S. E. Wenzel3, A. Menzies-Gow4, M. Wechsler5, J. Johnston6, J. Downie7, J. R. Parnes7, A. Megally8, G. Colice8, C. E. Brightling1; 1NIHR Biomedical Research Centre, Leicester, United Kingdom, 2Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, United States, 3University of Pittsburgh Asthma Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, United States, 4Royal Brompton Hospital, London, United Kingdom, 5National Jewish Health, Denver, CO, United States, 6Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, 7Amgen, Thousand Oaks, CA, United States, 8Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE: Patients with severe, uncontrolled asthma, particularly those with type 2 (T2)-low inflammatory phenotypes, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in the initiation and persistence of airway inflammation in response to airborne triggers of asthma such as viruses, allergens, pollutants and other airborne irritants. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating its effects on airway inflammatory cells and airway remodeling in patients with moderate-to-severe, uncontrolled asthma across the spectrum of T2 inflammatory phenotypes. This study is running concurrently with the NAVIGATOR and SOURCE phase 3 studies of tezepelumab, to support the clinical findings of those studies.
METHODS: CASCADE is an exploratory, phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in adults aged 18–75 years with moderate-to-severe, uncontrolled asthma (NCT03688074). In total, 116 patients from 27 sites across five countries, selected via a capping approach to span a range of blood eosinophil counts at screening (26% with <150 cells/μL, 34% with 150 to <300 cells/μL and 40% with ≥300 cells/μL), have been randomized 1:1 to receive tezepelumab 210 mg or placebo administered subcutaneously every 4 weeks over a 28-week treatment period, in addition to their prescribed controller medication (Figure). The primary endpoint is the change from baseline (pre-dose) to end of treatment in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Secondary outcomes include assessments of reticular basement membrane thickening, percentage airway epithelial integrity, and safety.
RESULTS: Results will be available in early 2021.
CONCLUSIONS: CASCADE evaluates the effect of tezepelumab on airway inflammatory cells and airway remodeling in a broad population of patients with moderate-to-severe, uncontrolled asthma and differing levels of T2 inflammation. The study aims to determine the mechanisms by which tezepelumab improves clinical outcomes in patients with moderate-to-severe asthma and further demonstrate its potential to reduce airway inflammation in patients with T2-high or T2-low asthma.
Author Block: S. E. Diver1, L. Khalfaoui1, C. Emson2, S. E. Wenzel3, A. Menzies-Gow4, M. Wechsler5, J. Johnston6, J. Downie7, J. R. Parnes7, A. Megally8, G. Colice8, C. E. Brightling1; 1NIHR Biomedical Research Centre, Leicester, United Kingdom, 2Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, United States, 3University of Pittsburgh Asthma Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, United States, 4Royal Brompton Hospital, London, United Kingdom, 5National Jewish Health, Denver, CO, United States, 6Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom, 7Amgen, Thousand Oaks, CA, United States, 8Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE: Patients with severe, uncontrolled asthma, particularly those with type 2 (T2)-low inflammatory phenotypes, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in the initiation and persistence of airway inflammation in response to airborne triggers of asthma such as viruses, allergens, pollutants and other airborne irritants. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating its effects on airway inflammatory cells and airway remodeling in patients with moderate-to-severe, uncontrolled asthma across the spectrum of T2 inflammatory phenotypes. This study is running concurrently with the NAVIGATOR and SOURCE phase 3 studies of tezepelumab, to support the clinical findings of those studies.
METHODS: CASCADE is an exploratory, phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in adults aged 18–75 years with moderate-to-severe, uncontrolled asthma (NCT03688074). In total, 116 patients from 27 sites across five countries, selected via a capping approach to span a range of blood eosinophil counts at screening (26% with <150 cells/μL, 34% with 150 to <300 cells/μL and 40% with ≥300 cells/μL), have been randomized 1:1 to receive tezepelumab 210 mg or placebo administered subcutaneously every 4 weeks over a 28-week treatment period, in addition to their prescribed controller medication (Figure). The primary endpoint is the change from baseline (pre-dose) to end of treatment in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Secondary outcomes include assessments of reticular basement membrane thickening, percentage airway epithelial integrity, and safety.
RESULTS: Results will be available in early 2021.
CONCLUSIONS: CASCADE evaluates the effect of tezepelumab on airway inflammatory cells and airway remodeling in a broad population of patients with moderate-to-severe, uncontrolled asthma and differing levels of T2 inflammation. The study aims to determine the mechanisms by which tezepelumab improves clinical outcomes in patients with moderate-to-severe asthma and further demonstrate its potential to reduce airway inflammation in patients with T2-high or T2-low asthma.
