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- Title
Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.
- Authors
Martinez, Fernando J.; Criner, Gerard J.; Gessner, Christian; Jandl, Margret; Scherbovsky, Fernando; Shinkai, Masaharu; Siler, Thomas M.; Vogelmeier, Claus F.; Voves, Robert; Wedzicha, Jadwiga A.; Bartels, Christian; Bottoli, Ivan; Byiers, Stuart; Cardenas, Pamela; Eckert, Joerg H.; Gutzwiller, Florian S.; Knorr, Barbara; Kothari, Mahavir; Parlikar, Rutvick; Tanase, Ana-Maria
- Abstract
Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction is associated with mucus accumulation and worsening chronic obstructive pulmonary disease (COPD) symptoms. Objectives: The aim of this phase IIb dose-finding study was to compare a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. Methods: Patients with COPD on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25mg or placebo twice daily [b.i.d.]) in a 24-week, multicenter, parallel-group, double-blind study. The primary endpoint was change from baseline in trough FEV1 after 12weeks. Secondary endpoints included change from baseline in trough FEV1 and Evaluating Respiratory Symptoms in COPD (E-RS) total and cough and sputum scores after 24weeks. Multiple comparison procedure-modeling was conducted to characterize dose-response relationship. Rescue medication use, exacerbations, and change in serum fibrinogen concentration after 24weeks were assessed in exploratory and post hoc analyses, respectively. Measurements and Main Results: Nine hundred seventy-four patients were randomized. After 12weeks of icenticaftor treatment, no dose-response relationship for change from baseline in trough FEV1 was observed; however, it was observed for E-RS cough and sputum score. A dose-response relationship was observed after 24weeks for trough FEV1, E-RS cough and sputum and total scores, rescue medication use, and fibrinogen. A dose of 300mg b.i.d. was consistently the most effective. Improvements for 300mg b.i.d. versus placebo were also seen in pairwise comparisons of these endpoints. All treatments were well tolerated. Conclusions: The primary endpoint was negative, as icenticaftor did not improve trough FEV1 over 12weeks. Although the findings must be interpreted with caution, icenticaftor improved trough FEV1; reduced cough, sputum, and rescue medication use; and lowered fibrinogen concentrations at 24weeks.
- Subjects
CYSTIC fibrosis transmembrane conductance regulator; SPUTUM examination; CHRONIC obstructive pulmonary disease; CHRONIC bronchitis
- Publication
American Journal of Respiratory & Critical Care Medicine, 2023, Vol 208, Issue 4, p417
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202303-0458OC