Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol.
<h4>Background</h4>Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to ke...
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Public Library of Science (PLoS)
2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0316721 |
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| author | Colin E Swenson William R Hunt Candela Manfredi Diana J Beltran Jeong S Hong Brian R Davis Shingo Suzuki Cristina Barillá Andras Rab Cynthia Chico Joy Dangerfield Ashleigh Streby Erin Barton Elizabeth M Cox Arlene A Stecenko Adrianna Westbrook Rebecca Kapolka Eric J Sorscher |
| author_facet | Colin E Swenson William R Hunt Candela Manfredi Diana J Beltran Jeong S Hong Brian R Davis Shingo Suzuki Cristina Barillá Andras Rab Cynthia Chico Joy Dangerfield Ashleigh Streby Erin Barton Elizabeth M Cox Arlene A Stecenko Adrianna Westbrook Rebecca Kapolka Eric J Sorscher |
| author_sort | Colin E Swenson |
| collection | DOAJ |
| description | <h4>Background</h4>Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to key features of cystic fibrosis (CF) lung disease. In CF, pathogenesis results from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), and diagnosis is made by demonstrating elevated sweat chloride concentrations (typically ≥60 mEq/L), two CFTR mutations known to be causal, multi-organ tissue injury, or combination(s) of these findings.<h4>Objective</h4>Based on a considerable body of evidence, we believe many patients with NCFBE have disease likely to benefit from drugs such as elexacaftor/tezacaftor/ivacaftor (ETI) that activate CFTR-dependent ion transport. ETI is currently prescribed solely for treatment of CF and has not been adequately tested or proposed for patients with NCFBE, many of whom exhibit decreased CFTR function. Accordingly, we are conducting a clinical trial of ETI in subjects carrying a diagnosis of NCFBE.<h4>Methods</h4>Participants will exhibit one disease-causing CFTR mutation and/or sweat chloride measurements of 30-59 mEq/L. Cutaneous punch biopsy or blood samples will be obtained for iPS cell differentiation into airway epithelial monolayers-which will then be tested for response to ETI. Each patient will be given CFTR modulator treatment for approximately four weeks, with monitoring of clinical endpoints that include FEV1 (forced expiratory volume in one second), sweat chloride, quality of life questionnaire, and weight. The study will evaluate response of patients with NCFBE to ETI, and test usefulness of iPSC-derived airway epithelial monolayers as a novel in vitro technology for predicting clinical benefit.<h4>Trial registration</h4>This trial is registered at clinicaltrials.gov (Identifier: NCT05743946. Date: 02/23/2023). |
| format | Article |
| id | doaj-art-5e434e85701a4c3da5ebd9bcfe8615c5 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-5e434e85701a4c3da5ebd9bcfe8615c52025-08-20T02:33:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031672110.1371/journal.pone.0316721Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol.Colin E SwensonWilliam R HuntCandela ManfrediDiana J BeltranJeong S HongBrian R DavisShingo SuzukiCristina BarilláAndras RabCynthia ChicoJoy DangerfieldAshleigh StrebyErin BartonElizabeth M CoxArlene A StecenkoAdrianna WestbrookRebecca KapolkaEric J Sorscher<h4>Background</h4>Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to key features of cystic fibrosis (CF) lung disease. In CF, pathogenesis results from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), and diagnosis is made by demonstrating elevated sweat chloride concentrations (typically ≥60 mEq/L), two CFTR mutations known to be causal, multi-organ tissue injury, or combination(s) of these findings.<h4>Objective</h4>Based on a considerable body of evidence, we believe many patients with NCFBE have disease likely to benefit from drugs such as elexacaftor/tezacaftor/ivacaftor (ETI) that activate CFTR-dependent ion transport. ETI is currently prescribed solely for treatment of CF and has not been adequately tested or proposed for patients with NCFBE, many of whom exhibit decreased CFTR function. Accordingly, we are conducting a clinical trial of ETI in subjects carrying a diagnosis of NCFBE.<h4>Methods</h4>Participants will exhibit one disease-causing CFTR mutation and/or sweat chloride measurements of 30-59 mEq/L. Cutaneous punch biopsy or blood samples will be obtained for iPS cell differentiation into airway epithelial monolayers-which will then be tested for response to ETI. Each patient will be given CFTR modulator treatment for approximately four weeks, with monitoring of clinical endpoints that include FEV1 (forced expiratory volume in one second), sweat chloride, quality of life questionnaire, and weight. The study will evaluate response of patients with NCFBE to ETI, and test usefulness of iPSC-derived airway epithelial monolayers as a novel in vitro technology for predicting clinical benefit.<h4>Trial registration</h4>This trial is registered at clinicaltrials.gov (Identifier: NCT05743946. Date: 02/23/2023).https://doi.org/10.1371/journal.pone.0316721 |
| spellingShingle | Colin E Swenson William R Hunt Candela Manfredi Diana J Beltran Jeong S Hong Brian R Davis Shingo Suzuki Cristina Barillá Andras Rab Cynthia Chico Joy Dangerfield Ashleigh Streby Erin Barton Elizabeth M Cox Arlene A Stecenko Adrianna Westbrook Rebecca Kapolka Eric J Sorscher Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. PLoS ONE |
| title | Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. |
| title_full | Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. |
| title_fullStr | Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. |
| title_full_unstemmed | Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. |
| title_short | Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol. |
| title_sort | evaluating elexacaftor tezacaftor ivacaftor eti trikafta™ for treatment of patients with non cystic fibrosis bronchiectasis ncfbe a clinical study protocol |
| url | https://doi.org/10.1371/journal.pone.0316721 |
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