Clinical trial NCT06350461: Impact of Discontinuing Hypertonic Saline in People With CF on Highly Effective CFTR Modulators- A SIMPLIFY Sub-Study
Official title: A Master Protocol to Test the Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy - Hypertonic Saline
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
CF
Withdrawal
ETI
hypertonic saline
discontinue
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: Dartmouth-Hitchcock Medical Center
name: University of Washington
First posted: 2024-04-05
Enrollment: 370
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies in treating cystic fibrosis (CF), it is still largely unknown whether or not other chronic therapies can be safely stopped. This SIMPLIFY sub-study is being done to test whether or not it is safe to stop taking inhaled hypertonic saline in those people that are also taking elexacaftor/tezacaftor/ivacaftor (ETI).

ETI 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 ETI 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 (HS) also improves clearance of mucus from the lungs to support lung function and has been available to people with CF for many years. HS is considered to be relatively burdensome and it is not known whether HS can improve or maintain lung function above what is already gained through ETI use.

The goal of this SIMPLIFY sub-study is to get information about whether or not it is safe to stop hypertonic saline by testing if there is a change in lung function in participants with cystic fibrosis (CF) who are assigned to stop taking HS as compared to those who are assigned to keep taking HS while continuing to take ETI.

This is a sub study of master protocol SIMPLIFY-IP-19, NCT04378153.

The sub study investigating the impact of discontinuing and continuing dornase alfa is registered under NCTXXXXXXX (will add once available).

Detailed description: This SIMPLIFY sub-study (Hypertonic Saline (HS) Trial) is designed to evaluate the effects of discontinuing HS in people with cystic fibrosis (CF) age 12 and older currently taking the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI). This is an open label two-arm randomized non-inferiority trial consisting of a 2-week screening period, randomization to continue or discontinue hypertonic saline, followed by a 6-week study period. Participants at trial entry will be randomized 1:1 to either continue or discontinue their HS therapy.

Clinical outcomes (forced expiratory volume in 1 second \[FEV1\], antibiotic use, pulmonary exacerbations, and patient reported outcomes), safety (adverse events) and patient reported outcomes to evaluate respiratory symptoms and the participant's perception of how stopping HS would impact their daily life will be evaluated in all subjects. Additionally, a subset of participants at selected study sites will participate in Multiple Breath Washout (MBW) to evaluate changes in lung clearance index (LCI).

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%) 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.

Primary outcomes:
measure: Absolute Change in FEV1 % Predicted From Week 0 to Week 6
timeFrame: Week 0 to Week 6
Secondary outcomes:
measure: Absolute Change in LCI 2.5 From Baseline to Week 6
timeFrame: Baseline (Week 0 or Week -2) to Week 6
measure: 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
timeFrame: Week 0 to Week 6
measure: Absolute Change in Respiratory Symptoms, as Measured by CFQ-R Respiratory Domain From Week 0 to Week 6
timeFrame: Week 0 to Week 6
measure: Absolute Change in FEV1 % Predicted From Week -2 to Week 0
timeFrame: Week -2 to Week 0
measure: Absolute Change in FEV1 % Predicted From Week 0 to Week 2
timeFrame: Week 0 to Week 2
measure: Number and Percent of Participants Initiating Acute Antibiotics From Week 0 to Week 6
timeFrame: Week 0 to Week 6
measure: Number and Percent of Participants Hospitalized From Week 0 to Week 6
timeFrame: Week 0 to Week 6
measure: Number and Percent of Participants Experiencing Pulmonary Exacerbations From Week 0 to Week 6
timeFrame: Week 0 to Week 6
measure: Number and Percent of Participants Experiencing Adverse Events (AEs) From Week 0 to Week 6
timeFrame: Week 0 to Week 6
measure: Rate of Adverse Events (AEs) From Week 0 to Week 6 Therapy Arms
timeFrame: Week 0 to Week 6
measure: Number and Percent of Participants With Temporary or Permanent Changes From Assigned Therapy Regimen Due to Adverse Event From Week 0 to Week 6
timeFrame: Week 0 to Week 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Tucson
country: United States
facility: Tucson Cystic Fibrosis Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Orange
country: United States
facility: CHOC Children's Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital and Health Center at the University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Adult Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco - Peds Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Orlando
country: United States
facility: The Nemours Children's Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boise
country: United States
facility: Saint Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Metairie
country: United States
facility: Tulane University
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Partners Pediatric Specialty Care
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Wayne State University Harper University Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Helen DeVos
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: The Minnesota Cystic Fibrosis Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Eatontown
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers - Robert Wood Johnson Medical School
state: New Jersey
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital Cystic Fibrosis Center
state: New York
city: New York
country: United States
facility: Columbia University Cystic Fibrosis Program
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center Strong Memorial
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College at Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cystic Fibrosis Program
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Hershey
country: United States
facility: Hershey Medical Center Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern / Children's Health
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Cystic Fibrosis Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Medical Group, Cystic Fibrosis Clinic
state: Washington
city: Morgantown
country: United States
facility: West Virginia University - Morgantown
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Washington/Seattle Children's
name: Nicole Mayer-Hamblett, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Alex Gifford, MD, FCCP
role: PRINCIPAL_INVESTIGATOR
References: