Current Environment:

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.

Conditions

Cystic Fibrosis

Recruitment Status

COMPLETED

Detailed Description

SIMPLIFY-IP-19 is a master protocol is designed to evaluate the independent effects of discontinuing hypertonic saline or dornase alfa in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). The hypertonic saline and dornase alfa sub studies are identical open label two-arm randomized non-inferiority trials consisting of a 2-week run-in period, randomization to continue or discontinue hypertonic saline or dornase alfa, 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 the hypertonic saline or dornase alfa 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. This clinicalrials.gov registration, NCT04378153, summarizes the 2-week run-in and adherence period prior to participant enrollment in either the Hypertonic Saline or Dornase Alfa sub studies. Two additional clincialtrials.gov records document the sub study specific enrollment and outcome measures. Hypertonic Saline Study Record * NCT06350461 * Brief Title: Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study (SIMPLIFY-HS) Dornase Alfa Study Record * NCT06350474 * Brief Title: Impact of Discontinuing Dornase Alfa in People With CF on Highly Effective CFTR Modulator Therapy-A SIMPLIFY Sub-Study (SIMPLIFY-DN)

Eligibility Criteria

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.

Gender

ALL

Min Age

12 Years

Max Age

N/A

Download Date

2024-09-23

Principal Investigator

N/A

Primary Contact Information

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team:

Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy NCT04378153