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

• ClinicalTrials.gov Identifier: NCT04378153
• Recruitment Status: Completed
• First Posted: May 7, 2020
• Last Update Posted: January 12, 2023
• Sponsor: Nicole Hamblett
• Collaborators: Cystic Fibrosis Foundation; Dartmouth-Hitchcock Medical Center; University of Washington
• Information provided by (Responsible Party): Nicole Hamblett, Seattle Children's Hospital

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Other: Discontinuation of hypertonic saline (HS); Other: Continuation of hypertonic saline (HS); Other: Discontinuation of dornase alfa (dnase); Other: Continuation of dornase alfa (dnase)	Not Applicable

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 870 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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)
• Actual Study Start Date: August 25, 2020
• Actual Primary Completion Date: July 11, 2022
• Actual Study Completion Date: July 11, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: HS-Discontinue (Study A); Discontinuation of current hypertonic saline (HS) therapy in Study A	Other: Discontinuation of hypertonic saline (HS); Discontinuation of current hypertonic saline (HS) therapy in Study A during 6-week study period.
Active Comparator: HS-Continue (Study A); Continuation of current hypertonic saline (HS) therapy in Study A	Other: Continuation of hypertonic saline (HS); 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%.
Experimental: Dnase-Discontinue (Study B); Discontinuation of current dornase alfa (dnase) therapy in Study B	Other: Discontinuation of dornase alfa (dnase); Discontinuation of current dornase alfa (dnase) therapy in Study B during 6-week study period.; Other Name: Discontinuation of pulmozyme
Active Comparator: Dnase-Continue (Study B); Continuation of current dornase alfa (dnase) therapy in Study B	Other: Continuation of dornase alfa (dnase); 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).; Other Name: Continuation of pulmozyme

Outcome Measures

Primary Outcome Measures :

1. Absolute change in FEV1 % predicted from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 6.
2. Absolute change in FEV1 % predicted from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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 :

1. Incidence of Adverse Events (AEs) in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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.
2. Incidence of Adverse Events (AEs) in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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.
3. 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 [ Time Frame: Week 0 to Week 6 ]
   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.
4. 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 Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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.
5. Absolute change in LCI 2.5 from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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.
6. Absolute change in LCI 2.5 from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
   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.
7. 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 [ Time Frame: Week 0 to Week 6 ]
   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.
8. 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 [ Time Frame: Week 0 to Week 6 ]
   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.
9. Absolute change in FEV1 % predicted from Week -2 to Week 0 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week -2 to Week 0 ]
   Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.
10. Absolute change in FEV1 % predicted from Week -2 to Week 0 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week -2 to Week 0 ]
    Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week -2 to Week 0.
11. Absolute change in FEV1 % predicted from Week 0 to Week 2 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 2 ]
    Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.
12. Absolute change in FEV1 % predicted from Week 0 to Week 2 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 2 ]
    Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the absolute change in FEV1 % predicted from Week 0 to Week 2.
13. Initiation of acute antibiotics from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
14. Initiation of acute antibiotics from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
15. Hospitalizations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    Difference between hypertonic saline (HS) therapy arms (HS-discontinue - HS-continue) in the percent of subjects hospitalized from Week 0 to Week 6
16. Hospitalizations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    Difference between dornase alfa (DA) therapy arms (DA-discontinue - DA-continue) in the percent of subjects hospitalized from Week 0 to Week 6
17. Pulmonary Exacerbations from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
18. Pulmonary exacerbations from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
19. Adverse events from Week 0 to Week 6 in Hypertonic Saline (Study A) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
20. Adverse events from Week 0 to Week 6 in Dornase Alfa (Study B) Therapy Arms [ Time Frame: Week 0 to Week 6 ]
    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
21. 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 [ Time Frame: Week 0 to Week 6 ]
    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
22. 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 [ Time Frame: Week 0 to Week 6 ]
    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

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Alaska

Providence Alaska Medical Center

Anchorage, Alaska, United States, 99508

United States, Arizona

Tucson Cystic Fibrosis Center

Tucson, Arizona, United States, 85724

United States, Arkansas

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202

United States, California

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States, 90806

CHOC Children's Hospital

Orange, California, United States, 92868

Stanford University Medical Center

Palo Alto, California, United States, 94304

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

San Diego, California, United States, 92123

University of California, San Francisco - Adult Center

San Francisco, California, United States, 94143

University of California, San Francisco - Peds Center

San Francisco, California, United States, 94158

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

National Jewish Health

Denver, Colorado, United States, 80206

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Nemours Children's Clinic

Jacksonville, Florida, United States, 32207

Central Florida Pulmonary Group

Orlando, Florida, United States, 32803

The Nemours Children's Clinic - Orlando

Orlando, Florida, United States, 32827

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States, 32514

All Children's Hospital

Saint Petersburg, Florida, United States, 33701

Tampa General Hospital

Tampa, Florida, United States, 33606

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30327

United States, Idaho

Saint Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States, 83702

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

OSF Saint Francis Medical Center

Peoria, Illinois, United States, 61637

United States, Indiana

Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40506

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Louisiana

Tulane University

Metairie, Louisiana, United States, 70001

United States, Maine

Maine Medical Partners Pediatric Specialty Care

Portland, Maine, United States, 04102

United States, Maryland

John Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Massachusetts

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

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan, Michigan Medicine

Ann Arbor, Michigan, United States, 48109

Wayne State University Harper University Hospital

Detroit, Michigan, United States, 48201

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States, 55404

The Minnesota Cystic Fibrosis Center

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Children's Mercy Kansas City

Kansas City, Missouri, United States, 64108

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Montana

Billings Clinic

Billings, Montana, United States, 59101

United States, New Hampshire

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Monmouth Medical Center

Eatontown, New Jersey, United States, 07724

Morristown Medical Center

Morristown, New Jersey, United States, 07960

Rutgers - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States, 08903

United States, New York

Cohen Children's Medical Center of New York

Lake Success, New York, United States, 11042

Beth Israel Medical Center

New York, New York, United States, 10003

Columbia University Cystic Fibrosis Program

New York, New York, United States, 10032

University of Rochester Medical Center Strong Memorial

Rochester, New York, United States, 14642

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

New York Medical College at Westchester Medical Center

Valhalla, New York, United States, 10595

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

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

Cleveland, Ohio, United States, 44146

Cleveland Clinic Cystic Fibrosis Program

Cleveland, Ohio, United States, 44195

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Dayton Children's Hospital

Dayton, Ohio, United States, 45404

United States, Oregon

Oregon Health Sciences University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Hershey Medical Center Pennsylvania State University

Hershey, Pennsylvania, United States, 17033

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15224

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

Dell Children's Medical Center of Central Texas

Austin, Texas, United States, 78723

University of Texas Southwestern / Children's Health

Dallas, Texas, United States, 75207

University of Texas Southwestern

Dallas, Texas, United States, 75390

Cook Children's Medical Center

Fort Worth, Texas, United States, 76104

University of Texas Health Center at Tyler

Tyler, Texas, United States, 75708

United States, Utah

Primary Children's Cystic Fibrosis Center

Salt Lake City, Utah, United States, 84113

United States, Vermont

University of Vermont Medical Center

Burlington, Vermont, United States, 05401

United States, Virginia

University of Virginia

Charlottesville, Virginia, United States, 22903

Virginia Commonwealth University

Richmond, Virginia, United States, 23219

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

University of Washington Medical Center

Seattle, Washington, United States, 98195

Providence Medical Group, Cystic Fibrosis Center

Spokane, Washington, United States, 99204

United States, West Virginia

West Virginia University - Morgantown

Morgantown, West Virginia, United States, 26507

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Nicole Hamblett

Cystic Fibrosis Foundation

Dartmouth-Hitchcock Medical Center

University of Washington

Investigators

• Principal Investigator: Nicole Mayer-Hamblett, PhD; University of Washington/Seattle Children's
• Principal Investigator: Alex Gifford, MD, FCCP; Dartmouth-Hitchcock Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Nicole Hamblett, Professor of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington School of Medicine Adjunct Professor, Biostatistics, University of Washington School of Medicine Co-Executive Director, Cystic Fibrosis Therapeutics Development, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT04378153
• Other Study ID Numbers: SIMPLIFY-IP-19
• First Posted: May 7, 2020
• Last Update Posted: January 12, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Nicole Hamblett, Seattle Children's Hospital:

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

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases