Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children

Study Overview
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Brief Summary
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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
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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 6 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 6 visits over a period of up to 3 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 one before ivacaftor or elex/tez/iva visit within 30 days before initiation of the therapy and five after ivacaftor or elex/tez/iva visits over a 24-month follow-up period.

Official Title
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A Prospective Study to Evaluate Biological and Clinical Effects of Significantly Corrected CFTR Function in Infants and Young Children (BEGIN Study)

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Ivacaftor or elexacaftor/tezacaftor/ivacaftor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Less than 5 years of age at the first study visit. Documentation of a CF diagnosis. Part B: Participated in Part A OR less than 6 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 180 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.

Ages Eligible for Study
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Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Part A<br>Children with CF not on ivacaftor or elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy. | |
| Part B<br>Children with CF planning to start ivacaftor or elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy. Participants from the Part A cohort of this study may enroll into the Part B cohort if they become eligible for these CFTR modulator therapies and plan to start them. | Drug: Ivacaftor or elexacaftor/tezacaftor/ivacaftor<br>* In Part B, approved CFTR modulator as prescribed at the discretion of the treating physician -not dictated by the BEGIN investigators<br>* Other names: Vertex (VX)-770 or VX-445/VX-661/VX-770;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A Primary Outcome Measure: Change in weight-for-age z-scores | Weight-for-age z-scores over time | Baseline to 12 months | 
| Part A Primary Outcome Measure: Change in height-for-age z-scores | Height-for-age z-scores over time | Baseline to 12 months | 
| Part B Primary Outcome Measure: Change in weight-for-age z-scores | Change in weight-for-age z-scores from baseline | 1, 3, 6, 12, and 24 months | 
| Part B Primary Outcome Measure: Change in height-for-age z-scores | Change in height-for-age z-scores from baseline | 1, 3, 6, 12, and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, CF, CFTR Modulator, triple combination therapy, elexacaftor, tezacaftor, ivacaftor