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Browse ATS 2021 Abstracts

HomeProgram ▶ Browse ATS 2021 Abstracts
 

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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Oral Dexpramipexole Efficacy in Lowering Blood Eosinophils in Patients with Moderate to Severe Uncontrolled Eosinophilic Asthma: Study Design and Baseline Data from the AS201 Phase 2 Trial

Session Title
TP6 - TP006 CLINICAL STUDIES OF ALLERGIC AIRWAY DISEASES, LUPUS, AND EOSINOPHILIC DISEASES
Abstract
A1359 - Oral Dexpramipexole Efficacy in Lowering Blood Eosinophils in Patients with Moderate to Severe Uncontrolled Eosinophilic Asthma: Study Design and Baseline Data from the AS201 Phase 2 Trial
Author Block: C. Prussin1, R. A. Panettieri2, M. E. Bozik1, D. G. Archibald1, J. L. Mather1, S. Siddiqui3; 1Knopp Biosciences, Pittsburgh, PA, United States, 2Institute for Translational Medicine and Science, Rutgers University, New Brunswick, NJ, United States, 3University of Leicester, Leicester, United Kingdom.
Rationale: Dexpramipexole is an oral small molecule drug that depletes eosinophils by inhibiting their maturation. In a previous study in chronic rhinosinusitis with nasal polyps and eosinophilia, dexpramipexole depleted both blood and tissue eosinophils by ≈95%. Approved anti-interleukin-5 biologics decrease asthma exacerbations by lowering eosinophils, suggesting dexpramipexole may be effective in asthma as an oral eosinophil-lowering drug. Here we present the study design and baseline data from the Phase 2 AS201 trial, evaluating the safety and efficacy of dexpramipexole when added to inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) therapy in patients with moderate-to-severe uncontrolled eosinophilic asthma. Methods: AS201 is an ongoing randomized, double-blind, placebo-controlled dose-ranging trial. Study entry criteria at screening include: asthmatic subjects ages 18-74 requiring at a minimum low-dose ICS/LABA, eosinophil count ≥0.30x109/L, forced expiratory volume in 1 second (FEV1) <80% predicted and 12% post-bronchodilator reversibility, and asthma control questionnaire (ACQ) score ≥1.5. Randomization is 1:1:1:1 placebo, dexpramipexole 75 mg/day, 150 mg/day, and 300 mg/day. The trial includes a placebo Run-in Phase, a 12-week Primary Assessment Phase, during which study drug is administered, and a 12-week Eosinophil Recovery Phase following study drug discontinuation. During the Run-in, subjects take placebo from a Smart Bottle and were required to demonstrate an adherence of ≥85% over a minimum 12-day period. The primary endpoint is change in blood absolute eosinophil count from Baseline to Week 12. Secondary endpoints include change from Baseline to Week 12 in pre-bronchodilator FEV1, Asthma Control Questionnaire (ACQ-6) score, post-bronchodilator FEV1, and Asthma Quality of Life Questionnaire. Exploratory Endpoints include change from Baseline in pharyngeal and nasal eosinophil peroxidase concentration, and eosinophil progenitors and basophils measured by flow cytometry. Results: 103 subjects were enrolled and randomized across 33 centers in the United States. Subjects had a mean age of 45 years, a 30-year mean duration of asthma, were 52% female, with racial distribution of 74% White, 19% Black or African American, and 3% Asian. Subjects’ Baseline Global Initiative for Asthma (GINA) severity class was distributed as follows: GINA 3 24%, GINA 4 55%, GINA 5 21%. Baseline mean ACQ-6 was 2.17. Baseline FEV1 was 2.06 L (62.1% predicted). Conclusion: The results of this study will characterize the eosinophil-lowering efficacy and dose response of dexpramipexole in patients with asthma and inform dose selection for Phase 3 trials. The study will further examine dexpramipexole safety and the kinetics of on-drug eosinophil lowering and off-drug eosinophil recovery.