Table 1.

Eligibility criteria for SIMPLIFY

Eligibility criteria at screening (Week −2). Eligibility criteria will be evaluated at the screening visit (Week −2) for each study in the protocol. Subjects who enter the SIMPLIFY master protocol receiving only hypertonic saline or only dornase alfa at the time of entry will only be eligible to participate in one study.

Consent

• Written informed consent (and assent when applicable) obtained from subject or subject's legal guardian

• Enrolled in the CF Patient Registry

• For the 6-wk study duration, willingness to either continue or discontinue daily use of hypertonic saline or dornase alfa (as applicable to study A or study B) based on randomization and according to the clinically prescribed routine (i.e., at least once daily)

• Is willing and able to adhere to the study-visit schedule and other protocol requirements, including willingness and ability to provide information using electronic questionnaires loaded onto a personal device (e.g., smartphone or tablet)

• For subjects who enter the SIMPLIFY master protocol receiving both hypertonic saline and dornase alfa at the time of entry into their first study: willingness to be randomized to either study A or study B

Demographics

• Age ⩾ 12 yr at the screening visit

Disease history

• Diagnosis of CF

• ppFEV1 ⩾ 70 at the screening visit if <18 yr old and ppFEV1 ⩾ 60 at screening visit if ⩾18 yr old

• After interim analysis, if the DMC approves, a separate cohort (lower-lung-function cohort) of approximately 120 subjects ⩾18 yr old with a ppFEV1 of 40 to <60 will be enrolled into study A.

• Clinically stable with no significant changes in health status within the 7 d prior to and including the screening visit

• No active smoking or vaping

• Has no other conditions that, in the opinion of the site investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study-outcome data, or otherwise interfere with achieving the study objectives

Concomitant medications and treatments

• Current treatment with ETI for at least the 90 d before and including the screening visit and willing to continue daily use for the duration of the study

• Currently receiving hypertonic saline (at least 3%) and/or dornase alfa for at least the 90 d before and including the screening visit and willing to continue daily use for the 2-wk screening period*

• Ability to tolerate albuterol or levalbuterol (Xopenex)

• No use of an investigational drug within the 28 d before and including the screening visit

• No changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within the 28 d before and including the screening visit. This includes new airway-clearance routines

• No acute use of antibiotics (oral, inhaled, or IV) or acute use of systemic corticosteroids for respiratory-tract symptoms within the 7 d before and including the screening visit

• No chronic use of systemic corticosteroids at a dose equivalent to ⩾10 mg/d of prednisone within the 28 d before and including the screening visit

• No antibiotic treatment for NTM within the 28 d before and including the screening visit

Eligibility criteria at randomization (Week 0). Eligibility criteria will be evaluated before randomization at visit 1 (Week 0) for each study.

Consent

• Is willing and able to adhere to the study-visit schedule and other protocol requirements

Disease history

• No absolute decrease in ppFEV1 ⩾10 between the screening visit and visit 1 (Week 0)

• Clinically stable with no significant changes in health status between the screening visit and visit 1 (Week 0)

Concomitant medications and treatments

• No acute use of antibiotics (oral, inhaled, or IV) or acute use of systemic corticosteroids for respiratory-tract symptoms from the screening visit to visit 1 (Week 0)

• More than 70% compliance with submission of daily ePRO questionnaires in the up to 13 d before visit 1 (Week 0)

• Among the daily ePRO questionnaires submitted in the up to 13 d before visit 1, at least 70% adherence with receiving ETI and, as applicable, hypertonic saline and/or dornase alfa, as reported from screening to visit 1 (Week 0)

Additional eligibility for MCC substudy

• Able to perform the testing and procedures required for the study, as judged by the investigator

• Able and willing to withhold hypertonic saline and dornase alfa for at least 12 h before each MCC scan at visits 1 (Week 0) and 3 (Week 6)

• Those able to become pregnant: negative pregnancy test at visit 1 (Week 0)

• Those able to become pregnant: able and willing to practice a medically acceptable form of contraception from 3 d before visit 1 (Week 0) through visit 3 (Week 6) (acceptable forms of contraception: hormonal birth control, intrauterine device, barrier method plus a spermicidal agent, or abstinence) unless surgically sterilized or postmenopausal

• No more than two chest CT scans in the 12 mo before visit 1 (Week 0) (or a combination of procedures that are believed to have exposed the subject’s lungs to >150 mSv for adults ⩾18 yr old or >15 mSv for children <18 yr old)

Definition of abbreviations: CF = cystic fibrosis; CT = computed tomography; DMC = data-monitoring committee; ePRO = electronic patient-reported outcome; ETI = elexacaftor/tezacaftor/ivacaftor; IV = intravenous; MCC = mucociliary clearance; NTM = nontuberculous mycobacteria; ppFEV₁ = percent-predicted forced expiratory volume in 1 second.

These eligibility criteria must be met for all participants, regardless of prior study participation.

^*For participants with prior participation in SIMPLIFY, subjects must continue with assigned use/nonuse of therapy in the prior trial or reestablish consistent hypertonic saline and/or dornase-alfa therapy before entering into the second study. There are no time constraints for reentering.