- Franssen FME, et al. Dose response of icenticaftor in patients with COPD and chronic bronchitis on triple inhaled therapy. ALERT 1, RCT710, ERS International Congress 2022, Barcelona, Spain, 4–6 September.
A phase 2b trial (NCT02449018), conducted by Prof. Frits Franssen (Maastricht University, the Netherlands) and co-investigators, assessed the dose-response relationship of icenticaftor on top of a triple therapy of long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS) in patients with COPD (GOLD 2 & 3) and chronic bronchitis (n=974). The trial included 5 icenticaftor arms, with doses ranging from 25 mg, twice daily, to 450 mg, twice daily, and a placebo arm. The primary endpoint was the change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 12.
The 450 mg arm of the study discontinued early for meeting a pre-specified, exposure-based stopping criterion. The 300 mg arm displayed the best efficacy results. Although the primary endpoint was not met, the 300 mg arm outperformed placebo with respect to trough FEV1 levels at 24 weeks (least-squares mean 35 mL, 90% CI 0.0008–0.062). Other endpoints showed similar results for the 300 mg arm after 24 weeks of therapy: change in EXACT-Respiratory Symptoms (E-RS) cough and sputum score (-0.40), E-RS total score (-0.85), fibrinogen (-0.332), number of daily puffs of rescue medication (-0.30).
No major safety concerns were observed for any of the treatment arms. Approximately 61% of the patients experienced at least 1 adverse event (AE), the most common being COPD exacerbations, diarrhoea, nausea, and nasopharyngitis.
Prof. Franssen emphasised that these results were obtained on top of maximum inhaled triple therapy. “The positive benefit-risk profile of the 300 mg, twice daily dose of icenticaftor supports further evaluation of this agent in patients with COPD and chronic bronchitis. Furthermore, we should look for a biomarker that helps us to select patients that are likely to benefit from additional icenticaftor.”