Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study

Absolute Change in FEV1 % Predicted From Week 0 to Week 6

Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator
 (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown
 whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is
 being done to test whether or not it is safe to stop taking inhaled hypertonic saline in
 those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI).
 
 ETI is a combination CFTR modulator therapy that was approved by the Food and Drug
 Administration for people with CF who have at least one F508del mutation. The three drugs
 that make up ETI work together to allow many more chloride ions to move into and out of the
 cells, improving the balance of salt and water in the lungs. These changes result in better
 clearance of mucus from the lungs and improvements in lung function.
 
 Inhaled hypertonic saline (HS) also improves clearance of mucus from the lungs to support
 lung function and has been available to people with CF for many years. HS is considered to be
 relatively burdensome and it is not known whether HS can improve or maintain lung function
 above what is already gained through ETI use.
 
 The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to
 stop hypertonic saline by testing if there is a change in lung function in participants with
 cystic fibrosis (CF) who are assigned to stop taking HS as compared to those who are assigned
 to keep taking HS while continuing to take ETI.
 
 This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153.
 
 The sub study investigating the impact of discontinuing and continuing dornase alfa is
 registered under NCTXXXXXXX (will add once available).