{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:17:22Z","timestamp":1791404242369,"version":"4.3.3"},"reference-count":26,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,3,10]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) was efficacious and safe in children aged 6\u201311\u2005years with cystic fibrosis (CF) heterozygous for <jats:italic>F508del<\/jats:italic> and a minimal function CF transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) variant (<jats:italic>F<\/jats:italic>\/MF genotypes) in a 24-week, placebo-controlled trial. We conducted a 96-week open-label extension study for children who completed the 24-week parent study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this phase 3b extension study, dosing was based on weight and age, with children weighing &lt;30\u2005kg and aged &lt;12\u2005years receiving ELX 100\u2005mg once daily, TEZ 50\u2005mg once daily and IVA 75\u2005mg every 12\u2005h, and children \u226530\u2005kg or \u226512\u2005years receiving ELX 200\u2005mg once daily, TEZ 100\u2005mg once daily and IVA 150\u2005mg every 12\u2005h. The primary end-point was safety and tolerability. Secondary and other efficacy end-points included absolute changes from parent study baseline in sweat chloride concentration, lung clearance index (LCI<jats:sub>2.5<\/jats:sub>), percentage predicted forced expiratory volume in 1\u2005s (FEV<jats:sub>1<\/jats:sub>) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 120 children were enrolled and dosed. 118 children (98.3%) had adverse events (AEs), which for most were mild (43.3%) or moderate (48.3%) in severity. The most common AEs (\u226520% of children) were COVID-19 (58.3%), cough (51.7%), nasopharyngitis (45.0%), pyrexia (40.0%), headache (37.5%), upper respiratory tract infection (30.8%), oropharyngeal pain (26.7%), rhinitis (24.2%), abdominal pain (22.5%) and vomiting (20.0%). Children who transitioned from the placebo and ELX\/TEZ\/IVA groups of the parent study had improvements from parent study baseline at Week 96 in mean sweat chloride concentration (\u221257.3 (95% CI \u221261.6\u2013\u2009\u221252.9) and \u221257.5 (95% CI \u221262.0\u2013\u2009\u221253.0) mmol\u00b7L<jats:sup>\u22121<\/jats:sup>), LCI<jats:sub>2.5<\/jats:sub> (\u22121.74 (95% CI \u22122.09\u2013\u2009\u22121.38) and \u22122.35 (95% CI \u22122.72\u2013\u2009\u22121.97)\u2005units), FEV<jats:sub>1<\/jats:sub> % pred (6.1 (95% CI 2.6\u20139.7) and 6.9 (95% CI 3.2\u201310.5) percentage points) and CFQ-R respiratory domain score (6.6 (95% CI 2.5\u201310.8) and 2.6 (95% CI \u22121.6\u20136.8)\u2005points).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ELX\/TEZ\/IVA treatment was generally safe and well tolerated, with a safety profile consistent with the parent study and older age groups. After starting ELX\/TEZ\/IVA, children had robust improvements in sweat chloride concentration and lung function that were maintained through 96\u2005weeks. These results demonstrate the safety and durable efficacy of ELX\/TEZ\/IVA in this paediatric population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1183\/13993003.02435-2024","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T08:00:25Z","timestamp":1744272025000},"page":"2402435","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Elexacaftor\/tezacaftor\/ivacaftor in children aged \u22656\u2005years with cystic fibrosis heterozygous for <i>F508del<\/i> and a minimal function mutation: results from a 96-week open-label extension study"],"prefix":"10.1183","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-3809","authenticated-orcid":false,"given":"Claire E.","family":"Wainwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Legg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Chilvers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Gartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-1025","authenticated-orcid":false,"given":"Anna-Maria","family":"Dittrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Stehling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Conner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Suresh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya G.","family":"Weinstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the VX20-445-119 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"2025071402250782000_66.1.2402435.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.23280"},{"key":"2025071402250782000_66.1.2402435.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2216474"},{"key":"2025071402250782000_66.1.2402435.3","unstructured":"Cystic Fibrosis Foundation . 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