A Phase IIb, Multicentre, Randomised, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Dirocaftor/Posenacaftor/Nesolicaftor in Subjects with Cystic Fibrosis Aged 18 Years or Older (CHOICES)

Prior treatment

• Subject is currently taking or has taken a CFTR modulator within 28 days prior to Day 1

• Male or female subjects who have completed the HIT-CF Organoid Study and are ≥18 years of age on the date of informed consent
• Confirmed diagnosis of CF as follows: Sweat chloride value of ≥60 mmol/L based on quantitative pilocarpine iontophoresis (at screening) OR 2-CF causing mutations AND o chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
• Clinically stable CF disease in the opinion of the investigator with no significant changes in health status within 28 days prior to Day 1
• FEV1 ≥40% to ≤90% predicted according to the Global Lung Function Initiative (GLI)
• Body mass index (BMI) ≥16 kg/m2 and ≤30 kg/m2
• Non-smoker and non-tobacco user for a minimum of 30 days prior to screening, and subject agrees not to smoke or use tobacco for the duration of the study
• Selected by an unblinded coordinating team based on organoid response or random selection