{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:40:09Z","timestamp":1793796009062,"version":"4.6.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":936,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged \u22656 years with at least one F508del-CFTR allele but has not been studied in younger children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX\/TEZ\/IVA in children with CF aged 2\u20135 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase 3, open-label, two-part study (parts A and B), children weighing &amp;lt;14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.5 mg each evening; children weighing \u226514 kg received ELX 100 mg qd, TEZ 50 mg qd, and IVA 75 mg every 12 hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The primary endpoints for part A (15-d treatment period) were pharmacokinetics and safety and tolerability. For part B (24-wk treatment period), the primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics and absolute changes from baseline in sweat chloride concentration and lung clearance index2.5 (LCI2.5, defined as the number of lung turnovers required to reduce the end tidal N2 concentration to 2.5% of its starting value) through Week 24. Analysis of pharmacokinetic data from 18 children enrolled in part A confirmed the appropriateness of the part B dosing regimen. In part B, 75 children (F508del\/minimal function genotypes, n\u2009=\u200952; F508del\/F508del genotype, n\u2009=\u200923) were enrolled and dosed. Seventy-four children (98.7%) had adverse events, which were all mild (62.7%) or moderate (36.0%) in severity. The most common adverse events were cough, fever, and rhinorrhea. Decreases in sweat chloride concentration (\u221257.9 mmol\/L; 95% confidence interval [CI], \u221261.3 to \u221254.6; n\u2009=\u200969) and LCI2.5 (\u22120.83 U; 95% CI, \u22121.01 to \u22120.66; n\u2009=\u200950) were observed from baseline through Week 24. Mean body mass index was within the normal range at baseline and remained stable at Week 24.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this open-label study in children 2\u20135 years of age, ELX\/TEZ\/IVA treatment was generally safe and well tolerated, with a safety profile consistent with that observed in older age groups, and led to clinically meaningful reductions in sweat chloride concentration and LCI2.5.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT04537793).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202301-0084oc","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T14:16:31Z","timestamp":1678889791000},"page":"59-67","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":149,"title":["Phase 3 Open-Label Clinical Trial of Elexacaftor\/Tezacaftor\/Ivacaftor in Children Aged 2\u20135 Years with Cystic Fibrosis and at Least One\n                    <i>F508del<\/i>\n                    Allele"],"prefix":"10.1093","volume":"208","author":[{"given":"Jennifer L.","family":"Goralski","sequence":"first","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordana E.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine and Children\u2019s Hospital Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"German Center for Lung Research, Associated Partner, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna A.","family":"McColley","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children\u2019s Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5455-8208","authenticated-orcid":false,"given":"Edward","family":"McKone","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, Seattle, Washington"},{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Rayment","sequence":"additional","affiliation":[{"name":"University of British Columbia and British Columbia Children\u2019s Hospital, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Robinson","sequence":"additional","affiliation":[{"name":"The Royal Children\u2019s Hospital, Murdoch Children\u2019s Research Institute, Melbourne, Victoria, Australia"},{"name":"Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Stehling","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-9722","authenticated-orcid":false,"given":"Jennifer L.","family":"Taylor-Cousar","sequence":"additional","affiliation":[{"name":"National Jewish Health, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tullis","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Inc., Boston, Massachusetts; 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