Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy

  • STATUS
    Recruiting
  • End date
    May 31, 2022
  • participants needed
    800
  • sponsor
    David Nichols, MD
Updated on 26 January 2021
pulmonary function test
fibrosis
forced expiratory volume
dornase alfa
cystic fibrosis transmembrane conductance regulator
ivacaftor
tezacaftor
pulmozyme
elexacaftor
dnase

Summary

Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating CF, it is still largely unknown whether or not other chronic therapies can be safely stopped. The SIMPLIFY study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline or Pulmozyme (dornase alfa) in those people that are also taking Trikafta.

Trikafta (elexacaftor/tezacaftor/ivacaftor) 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 Trikafta 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 and Pulmozyme (dornase alfa) also improve clearance of mucus from the lungs to support lung function and have been available to people with CF for many years. Both therapies are considered to be relatively burdensome and it is not known whether either therapy can improve or maintain lung function above what is already gained through Trikafta use.

The goal of the SIMPLIFY study is to get information about whether or not it is safe to stop either inhaled hypertonic saline or Pulmozyme (dornase alfa) by testing if there is a change in lung function in subjects with cystic fibrosis (CF) who are assigned to stop their chronic medication (either hypertonic saline or Pulmozyme) as compared to those who are assigned to keep taking their medication while continuing to take Trikafta.

Description

This master protocol is designed to evaluate the independent effects of discontinuing hypertonic saline (Study A) and dornase alfa (Study B) in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). Study A and Study B are identical open label two-arm randomized non-inferiority trials consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline (Study A) or dornase alfa (Study B), followed by a 6-week study period. Subjects taking only hypertonic saline (HS) or dornase alfa at trial entry will be randomized 1:1 to either continue or discontinue the applicable therapy (i.e. HS or dornase alfa). Subjects taking both hypertonic saline and dornase alfa at study entry will be randomized to participate in either Study A or Study B and will be randomized (1:1) to continue or discontinue the applicable therapy (i.e. HS or dornase alfa). After completion of the first study, eligible subjects may subsequently enroll in the alternative study.

Clinical outcomes (forced expiratory volume in 1 second [FEV1], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and the subject's perception of how stopping HS or dornase alfa (or both) would impact their daily life will be evaluated in all subjects. Additional outcome measurements will be conducted in a subset of subjects at selected study sites:

  • Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI)
  • Mucociliary Clearance (MCC) using inhaled radio-labeled particles to evaluate changes in mucociliary clearance

Details
Condition Pulmonary Disease, Cystic Fibrosis, Pancreatic disorder, Pancreatic Disorders, Lung Disease
Treatment Discontinuation of hypertonic saline (HS), Continuation of hypertonic saline (HS), Discontinuation of dornase alfa (dnase), Continuation of dornase alfa (dnase)
Clinical Study IdentifierNCT04378153
SponsorDavid Nichols, MD
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of CF
Age 12 years at the Screening Visit
Forced expiratory volume in 1 second (FEV1) 70 % predicted at the Screening Visit if < 18 years old, and 60 % predicted at Screening Visit if 18 years old
Clinically stable with no significant changes in health status within the 7 days prior to and including the Screening Visit
Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the duration of the study
Currently taking hypertonic saline (at least 3%) and/or dornase alfa for at least the 90 days prior to and including the Screening Visit and willing to continue daily use for the 2-week screening period

Exclusion Criteria

Active smoking or vaping
Use of an investigational drug within 28 days prior to and including the Screening Visit
Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, aztreonam lysine) within 28 days prior to and including the Screening Visit. This includes new airway clearance routines
Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract symptoms within 7 days prior to and including the Screening Visit
Chronic use of systemic corticosteroids at a dose equivalent to 10mg per day of prednisone within 28 days prior to and including the Screening Visit
Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and including the Screening Visit
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