This SIMPLIFY sub-study (Dornase Alfa (Dnase) Trial) is designed to evaluate the effects of discontinuing Dnase in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). This is an open label two-arm randomized non-inferiority trial consisting of a 2-week screening period, randomization to continue or discontinue dornase alfa, followed by a 6-week study period. Participants at trial entry will be randomized 1:1 to either continue or discontinue their Dnase therapy.
Clinical outcomes (forced expiratory volume in 1 second \[FEV1\], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and patient reported outcomes to evaluate respiratory symptoms and the participant's perception of how stopping Dnase would impact their daily life will be evaluated in all subjects. Additionally, a subset of participants at selected study sites will participate in Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI).
