Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.
Academic Article
Overview
abstract
RATIONALE: CF transmembrane conductance regulator (CFTR) dysfunction is associated with mucus accumulation and worsening COPD symptoms. This Phase 2b dose-finding study compared a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. METHODS: COPD patients on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25mg or placebo b.i.d.) in a 24-week, multicenter, parallel-group, double-blind study. The primary endpoint was change from baseline in trough FEV1 after 12 weeks. Secondary endpoints included change from baseline in trough FEV1, Evaluating Respiratory Symptoms in COPD (E-RS) total and cough and sputum scores after 24 weeks. Multiple Comparison Procedure-Modelling characterized dose-response. Rescue medication use, exacerbations, and change in serum fibrinogen levels after 24 weeks were exploratory and post-hoc analyses, respectively. MeasurementsandMainResults:974 patients were randomized.After 12 weeks of icenticaftor treatment, no dose-response for change from baseline in trough FEV1 was observed; however, it was observed for E-RS cough and sputum score. A dose-response was observed after 24 weeks for trough FEV1, E-RS cough and sputum and total scores, rescue medication use and fibrinogen. 300mg b.i.d. was consistently the most effective dose. 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 12 weeks. Although the findings must be interpreted with caution, icenticaftor improved trough FEV1, cough, sputum, rescue medication use and lowered fibrinogen levels at 24 weeks. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT04072887.
