Clinical trial NCT04509050: Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children
Official title: A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function in Infants and Young Children (BEGIN Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
CF
CFTR Modulator
triple combination therapy
elexacaftor
tezacaftor
ivacaftor
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: University of Washington
name: University of Alabama at Birmingham
First posted: 2020-08-11
Enrollment: 210
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Part A - children with confirmed diagnosis of cystic fibrosis who are less than 10 years of age and not on ivacaftor or elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy

Part B - children with confirmed diagnosis of cystic fibrosis who are less than 7 years of age (or participated in Part A of the study) with an intention to start ivacaftor or elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy

Brief summary: This is a two-part, multi-center, prospective longitudinal, exploratory study of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their impact on children with cystic fibrosis (CF).

Detailed description: This is a two-part, multi-center, prospective longitudinal, exploratory study of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their impact in children with cystic fibrosis (CF) on endocrine growth factors and height, gastrointestinal function and gut microbiome, lung function and respiratory microbiome, liver and pancreatic function, sweat chloride, inflammatory markers, and bone health.

Total duration of the study is expected to be 10 years. Part A will be a prospective cross-sequential study to describe the natural history of hormonal growth factors in early childhood and assess the feasibility of additional measurements. In Part A, subjects will have up to 8 visits over a period of up to 5 years.

Part B will be a prospective longitudinal study to observe the effects of administration of either ivacaftor or elexacaftor/tezacaftor/ivacaftor (elex/tez/iva) on growth. In Part B, subjects will have 1 "before ivacaftor or elex/tez/iva" visit within 30 days before initiation of the therapy and 8 "after ivacaftor or elex/tez/iva" visits over a 60-month follow-up period.

Eligibility criteria: Inclusion Criteria:

* Part A:

  * Less than 10 years of age at the first study visit.
  * Documentation of a CF diagnosis.

Part B:

* Participated in Part A OR less than 7 years of age at the first study visit.
* Documentation of a CF diagnosis.
* CFTR mutations consistent with FDA labeled indication of highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor).
* Physician intent to prescribe ivacaftor or elexacaftor/tezacaftor/ivacaftor.

Exclusion Criteria:

* Part A and Part B:
* Use of an investigational drug within 28 days prior to and including the first study visit.
* Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 28 days prior to and including the first study visit.
* Use of chronic oral corticosteroids within the 28 days prior to and including the first study visit.

Primary outcomes:
measure: Part A Primary Outcome Measure: Change in weight-for-age z-scores
timeFrame: Baseline to 12 months
measure: Part A Primary Outcome Measure: Change in height-for-age z-scores
timeFrame: Baseline to 12 months
measure: Part B Primary Outcome Measure: Change in weight-for-age z-scores
timeFrame: Baseline to 12 months
measure: Part B Primary Outcome Measure: Change in height-for-age z-scores
timeFrame: Baseline to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Children's Hospital Alabama, University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: The Nemours Children's Clinic - Orlando
state: Florida
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: 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: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
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: St. Louis Children's Hospital
state: Missouri
city: Buffalo
country: United States
facility: The Cystic Fibrosis Center of Western New York
state: New York
city: New York
country: United States
facility: Children's Hospital of New York
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: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cystic Fibrosis Center
state: Oklahoma
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: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern / Children's Health
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Cystic Fibrosis Center
state: Utah
city: Burlington
country: United States
facility: Vermont Children's Hospital
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Seattle Children's Hospital
name: Bonnie Ramsey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington/Seattle Children's
name: Lucas Hoffman, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Katie Larson Ode, MD
role: PRINCIPAL_INVESTIGATOR
References: