Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.

Area of Science:

• Pulmonary Medicine
• Respiratory Diseases
• Pharmacology

Background:

• Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction is linked to mucus buildup and exacerbation of Chronic Obstructive Pulmonary Disease (COPD) symptoms.
• CFTR potentiators represent a potential therapeutic strategy for managing COPD and chronic bronchitis.

Purpose of the Study:

• To evaluate the efficacy and safety of icenticaftor (QBW251), a novel CFTR potentiator, in a Phase IIb dose-finding study.
• To compare various doses of icenticaftor against a placebo in patients with COPD and chronic bronchitis.

Main Methods:

• A 24-week, multicenter, double-blind, randomized study involving 974 COPD patients on triple therapy.
• Patients received icenticaftor (25-450 mg) or placebo twice daily (b.i.d.).
• Primary endpoint: change in trough FEV1 at 12 weeks; secondary endpoints included respiratory symptom scores (E-RS) and FEV1 at 24 weeks.

Main Results:

• No significant dose-response relationship for trough FEV1 was observed at 12 weeks.
• A dose-response relationship emerged at 24 weeks for trough FEV1, E-RS cough and sputum scores, rescue medication use, and serum fibrinogen.
• The 300 mg b.i.d. dose demonstrated consistent efficacy across multiple endpoints compared to placebo.

Conclusions:

• Icenticaftor did not meet the primary endpoint of improving trough FEV1 at 12 weeks.
• Despite the initial negative primary endpoint, icenticaftor showed potential benefits at 24 weeks, including improved FEV1, reduced respiratory symptoms, and lower fibrinogen levels.
• The 300 mg b.i.d. dose was identified as the most effective, and all tested doses were well-tolerated.