Back to results

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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Discontinuation of hypertonic saline (HS)

Continuation of hypertonic saline (HS)

Discontinuation of dornase alfa (dnase)

Continuation of dornase alfa (dnase)

About this trial

This is an interventional other trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, CF, Withdrawal, Trikafta, hypertonic saline, dornase alfa, pulmozyme

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Alabama at Birmingham
Providence Alaska Medical Center
Tucson Cystic Fibrosis Center
Arkansas Children's Hospital
Miller Children's and Women's Hospital Long Beach
CHOC Children's Hospital
Stanford University Medical Center
Rady Children's Hospital and Health Center at the University of California San Diego
University of California, San Francisco - Adult Center
University of California, San Francisco - Peds Center
Children's Hospital Colorado
National Jewish Health
Yale University School of Medicine
University of Florida
Nemours Children's Clinic
Central Florida Pulmonary Group
The Nemours Children's Clinic - Orlando
Nemours Children's Clinic - Pensacola
All Children's Hospital
Tampa General Hospital
Emory University
Saint Luke's Cystic Fibrosis Center of Idaho
Northwestern University
OSF Saint Francis Medical Center
Riley Hospital for Children
University of Iowa
University of Kansas Medical Center
University of Kentucky
University of Louisville
Tulane University
Maine Medical Partners Pediatric Specialty Care
John Hopkins Hospital
Boston Children's Hospital, Brigham & Women's Hospital
University of Michigan, Michigan Medicine
Wayne State University Harper University Hospital
Helen DeVos Children's Hospital
Children's Hospitals and Clinics of Minnesota
The Minnesota Cystic Fibrosis Center
Children's Mercy Kansas City
Washington University School of Medicine
Billings Clinic
Dartmouth Hitchcock Medical Center
Monmouth Medical Center
Morristown Medical Center
Rutgers - Robert Wood Johnson Medical School
Cohen Children's Medical Center of New York
Beth Israel Medical Center
Columbia University Cystic Fibrosis Program
University of Rochester Medical Center Strong Memorial
SUNY Upstate Medical University
New York Medical College at Westchester Medical Center
University of North Carolina at Chapel Hill
Wake Forest University Baptist Medical Center
Children's Hospital Medical Center of Akron
Cincinnati Children's Hospital Medical Center
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland Clinic Cystic Fibrosis Program
Nationwide Children's Hospital
Dayton Children's Hospital
Oregon Health Sciences University
Hershey Medical Center Pennsylvania State University
University of Pennsylvania
University of Pittsburgh Medical Center
Medical University of South Carolina
Dell Children's Medical Center of Central Texas
University of Texas Southwestern / Children's Health
University of Texas Southwestern
Cook Children's Medical Center
University of Texas Health Center at Tyler
Primary Children's Cystic Fibrosis Center
University of Vermont Medical Center
University of Virginia
Virginia Commonwealth University
Seattle Children's Hospital
University of Washington Medical Center
Providence Medical Group, Cystic Fibrosis Center
West Virginia University - Morgantown
University of Wisconsin
Children's Hospital of Wisconsin
Froedtert & Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

HS-Discontinue (Study A)

HS-Continue (Study A)

Dnase-Discontinue (Study B)

Dnase-Continue (Study B)

Arm Description

Discontinuation of current hypertonic saline (HS) therapy in Study A

Continuation of current hypertonic saline (HS) therapy in Study A

Discontinuation of current dornase alfa (dnase) therapy in Study B

Continuation of current dornase alfa (dnase) therapy in Study B

Outcomes

Primary Outcome Measures

Absolute change in FEV1 % predicted from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Absolute change in FEV1 % predicted from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Secondary Outcome Measures

Incidence of Adverse Events (AEs) in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.

Incidence of Adverse Events (AEs) in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.

Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.

Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the absolute change in respiratory symptoms, as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CRISS) from Week 0 to Week 6. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.

Absolute change in LCI 2.5 from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Week 0 to Week 6.

Absolute change in LCI 2.5 from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Week 0 to Week 6.

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants from 3 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in respiratory symptoms, as measured by the Cystic Fibrosis Questionnaire-Revised Respiratory Domain Score from Week 0 to Week 6. The Cystic Fibrosis Questionnaire - Revised asks participants from 3 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.

Absolute change in FEV1 % predicted from Week -2 to Week 0 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Absolute change in FEV1 % predicted from Week -2 to Week 0 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Absolute change in FEV1 % predicted from Week 0 to Week 2 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Absolute change in FEV1 % predicted from Week 0 to Week 2 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Initiation of acute antibiotics from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6

Initiation of acute antibiotics from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6

Hospitalizations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects hospitalized from Week 0 to Week 6

Hospitalizations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects hospitalized from Week 0 to Week 6

Pulmonary Exacerbations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6

Pulmonary exacerbations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6

Adverse events from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6

Adverse events from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6

Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6

Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects temporarily or permanently changing their assigned therapy regimen due to an adverse event Week 0 to Week 6

Full Information

NCT ID

NCT04378153

First Posted

May 4, 2020

Last Updated

January 10, 2023

Sponsor

Nicole Hamblett

Collaborators

Cystic Fibrosis Foundation, Dartmouth-Hitchcock Medical Center, University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT04378153

Brief Title

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

Acronym

SIMPLIFY

Official Title

A Master Protocol to Test the Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy (SIMPLIFY)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

August 25, 2020 (Actual)

Primary Completion Date

July 11, 2022 (Actual)

Study Completion Date

July 11, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Nicole Hamblett

Collaborators

Cystic Fibrosis Foundation, Dartmouth-Hitchcock Medical Center, University of Washington

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

Cystic Fibrosis, CF, Withdrawal, Trikafta, hypertonic saline, dornase alfa, pulmozyme

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

870 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HS-Discontinue (Study A)

Arm Type

Experimental

Arm Description

Discontinuation of current hypertonic saline (HS) therapy in Study A

Arm Title

HS-Continue (Study A)

Arm Type

Active Comparator

Arm Description

Continuation of current hypertonic saline (HS) therapy in Study A

Arm Title

Dnase-Discontinue (Study B)

Arm Type

Experimental

Arm Description

Discontinuation of current dornase alfa (dnase) therapy in Study B

Arm Title

Dnase-Continue (Study B)

Arm Type

Active Comparator

Arm Description

Continuation of current dornase alfa (dnase) therapy in Study B

Intervention Type

Other

Intervention Name(s)

Discontinuation of hypertonic saline (HS)

Intervention Description

Discontinuation of current hypertonic saline (HS) therapy in Study A during 6-week study period.

Intervention Type

Other

Intervention Name(s)

Continuation of hypertonic saline (HS)

Intervention Description

Continuation of current hypertonic saline (HS) therapy in Study A during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily). The concentration of HS is according to clinical prescription (e.g., 7% sodium chloride or 3.5% sodium chloride) and at least 3%.

Intervention Type

Other

Intervention Name(s)

Discontinuation of dornase alfa (dnase)

Other Intervention Name(s)

Discontinuation of pulmozyme

Intervention Description

Discontinuation of current dornase alfa (dnase) therapy in Study B during 6-week study period.

Intervention Type

Other

Intervention Name(s)

Continuation of dornase alfa (dnase)

Other Intervention Name(s)

Continuation of pulmozyme

Intervention Description

Continuation of current dornase alfa (dnase) therapy in Study B during 6-week study period. Therapy is taken at least once daily according to each participant's pre-existing, clinically prescribed regimen (e.g., daily, twice daily).

Primary Outcome Measure Information:

Title

Absolute change in FEV1 % predicted from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Title

Absolute change in FEV1 % predicted from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Secondary Outcome Measure Information:

Title

Incidence of Adverse Events (AEs) in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Title

Incidence of Adverse Events (AEs) in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (dnase) therapy arms (dnase-discontinue - dnase-continue) in the proportion of participants with at least one AE from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Title

Description

Time Frame

Week 0 to Week 6

Title

Description

Time Frame

Week 0 to Week 6

Title

Absolute change in LCI 2.5 from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Title

Absolute change in LCI 2.5 from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in LCI 2.5 (Lung Clearance Index) from Week 0 to Week 6.

Time Frame

Week 0 to Week 6

Title

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Time Frame

Week 0 to Week 6

Title

Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Time Frame

Week 0 to Week 6

Title

Absolute change in FEV1 % predicted from Week -2 to Week 0 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Time Frame

Week -2 to Week 0

Title

Absolute change in FEV1 % predicted from Week -2 to Week 0 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.

Time Frame

Week -2 to Week 0

Title

Absolute change in FEV1 % predicted from Week 0 to Week 2 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Time Frame

Week 0 to Week 2

Title

Absolute change in FEV1 % predicted from Week 0 to Week 2 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.

Time Frame

Week 0 to Week 2

Title

Initiation of acute antibiotics from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Initiation of acute antibiotics from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects initiating acute oral, inhaled or intravenous antibiotics from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Hospitalizations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects hospitalized from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Hospitalizations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects hospitalized from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Pulmonary Exacerbations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Pulmonary exacerbations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing a pulmonary exacerbation from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Adverse events from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Adverse events from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects experiencing an adverse event from Week 0 to Week 6

Time Frame

Week 0 to Week 6

Title

Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms

Description

Time Frame

Week 0 to Week 6

Title

Temporary or permanent changes from assigned therapy regimen due to adverse event from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms

Description

Time Frame

Week 0 to Week 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicole Mayer-Hamblett, PhD

Organizational Affiliation

University of Washington/Seattle Children's

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alex Gifford, MD, FCCP

Organizational Affiliation

Dartmouth-Hitchcock Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Providence Alaska Medical Center

City

Anchorage

State/Province

Alaska

ZIP/Postal Code

99508

Country

United States

Facility Name

Tucson Cystic Fibrosis Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

Facility Name

Arkansas Children's Hospital

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72202

Country

United States

Facility Name

Miller Children's and Women's Hospital Long Beach

City

Long Beach

State/Province

California

ZIP/Postal Code

90806

Country

United States

Facility Name

CHOC Children's Hospital

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Stanford University Medical Center

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

Rady Children's Hospital and Health Center at the University of California San Diego

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

University of California, San Francisco - Adult Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

University of California, San Francisco - Peds Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

Facility Name

Children's Hospital Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

National Jewish Health

City

Denver

State/Province

Colorado

ZIP/Postal Code

80206

Country

United States

Facility Name

Yale University School of Medicine

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

University of Florida

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

Facility Name

Nemours Children's Clinic

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32207

Country

United States

Facility Name

Central Florida Pulmonary Group

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

The Nemours Children's Clinic - Orlando

City

Orlando

State/Province

Florida

ZIP/Postal Code

32827

Country

United States

Facility Name

Nemours Children's Clinic - Pensacola

City

Pensacola

State/Province

Florida

ZIP/Postal Code

32514

Country

United States

Facility Name

All Children's Hospital

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33701

Country

United States

Facility Name

Tampa General Hospital

City

Tampa

State/Province

Florida

ZIP/Postal Code

33606

Country

United States

Facility Name

Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30327

Country

United States

Facility Name

Saint Luke's Cystic Fibrosis Center of Idaho

City

Boise

State/Province

Idaho

ZIP/Postal Code

83702

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

OSF Saint Francis Medical Center

City

Peoria

State/Province

Illinois

ZIP/Postal Code

61637

Country

United States

Facility Name

Riley Hospital for Children

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Facility Name

University of Kentucky

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40506

Country

United States

Facility Name

University of Louisville

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Tulane University

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70001

Country

United States

Facility Name

Maine Medical Partners Pediatric Specialty Care

City

Portland

State/Province

Maine

ZIP/Postal Code

04102

Country

United States

Facility Name

John Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Boston Children's Hospital, Brigham & Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

University of Michigan, Michigan Medicine

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Wayne State University Harper University Hospital

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Helen DeVos Children's Hospital

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

Children's Hospitals and Clinics of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55404

Country

United States

Facility Name

The Minnesota Cystic Fibrosis Center

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Children's Mercy Kansas City

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108

Country

United States

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Billings Clinic

City

Billings

State/Province

Montana

ZIP/Postal Code

59101

Country

United States

Facility Name

Dartmouth Hitchcock Medical Center

City

Lebanon

State/Province

New Hampshire

ZIP/Postal Code

03756

Country

United States

Facility Name

Monmouth Medical Center

City

Eatontown

State/Province

New Jersey

ZIP/Postal Code

07724

Country

United States

Facility Name

Morristown Medical Center

City

Morristown

State/Province

New Jersey

ZIP/Postal Code

07960

Country

United States

Facility Name

Rutgers - Robert Wood Johnson Medical School

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08903

Country

United States

Facility Name

Cohen Children's Medical Center of New York

City

Lake Success

State/Province

New York

ZIP/Postal Code

11042

Country

United States

Facility Name

Beth Israel Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10003

Country

United States

Facility Name

Columbia University Cystic Fibrosis Program

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

University of Rochester Medical Center Strong Memorial

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

SUNY Upstate Medical University

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210

Country

United States

Facility Name

New York Medical College at Westchester Medical Center

City

Valhalla

State/Province

New York

ZIP/Postal Code

10595

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Facility Name

Wake Forest University Baptist Medical Center

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

Facility Name

Children's Hospital Medical Center of Akron

City

Akron

State/Province

Ohio

ZIP/Postal Code

44308

Country

United States

Facility Name

Cincinnati Children's Hospital Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44146

Country

United States

Facility Name

Cleveland Clinic Cystic Fibrosis Program

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Nationwide Children's Hospital

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205

Country

United States

Facility Name

Dayton Children's Hospital

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45404

Country

United States

Facility Name

Oregon Health Sciences University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Hershey Medical Center Pennsylvania State University

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

Dell Children's Medical Center of Central Texas

City

Austin

State/Province

Texas

ZIP/Postal Code

78723

Country

United States

Facility Name

University of Texas Southwestern / Children's Health

City

Dallas

State/Province

Texas

ZIP/Postal Code

75207

Country

United States

Facility Name

University of Texas Southwestern

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Facility Name

Cook Children's Medical Center

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

University of Texas Health Center at Tyler

City

Tyler

State/Province

Texas

ZIP/Postal Code

75708

Country

United States

Facility Name

Primary Children's Cystic Fibrosis Center

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84113

Country

United States

Facility Name

University of Vermont Medical Center

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05401

Country

United States

Facility Name

University of Virginia

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23219

Country

United States

Facility Name

Seattle Children's Hospital

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

University of Washington Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

Facility Name

Providence Medical Group, Cystic Fibrosis Center

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

Facility Name

West Virginia University - Morgantown

City

Morgantown

State/Province

West Virginia

ZIP/Postal Code

26507

Country

United States

Facility Name

University of Wisconsin

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

Facility Name

Children's Hospital of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

Facility Name

Froedtert & Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36343646

Citation

Mayer-Hamblett N, Ratjen F, Russell R, Donaldson SH, Riekert KA, Sawicki GS, Odem-Davis K, Young JK, Rosenbluth D, Taylor-Cousar JL, Goss CH, Retsch-Bogart G, Clancy JP, Genatossio A, O'Sullivan BP, Berlinski A, Millard SL, Omlor G, Wyatt CA, Moffett K, Nichols DP, Gifford AH; SIMPLIFY Study Group. Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials. Lancet Respir Med. 2023 Apr;11(4):329-340. doi: 10.1016/S2213-2600(22)00434-9. Epub 2022 Nov 4.

Results Reference

derived

PubMed Identifier

33735508

Citation

Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.

Results Reference

derived

PubMed Identifier

33465316

Citation

Mayer-Hamblett N, Nichols DP, Odem-Davis K, Riekert KA, Sawicki GS, Donaldson SH, Ratjen F, Konstan MW, Simon N, Rosenbluth DB, Retsch-Bogart G, Clancy JP, VanDalfsen JM, Buckingham R, Gifford AH. Evaluating the Impact of Stopping Chronic Therapies after Modulator Drug Therapy in Cystic Fibrosis: The SIMPLIFY Clinical Trial Study Design. Ann Am Thorac Soc. 2021 Aug;18(8):1397-1405. doi: 10.1513/AnnalsATS.202010-1336SD.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs