{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T22:35:15Z","timestamp":1794090915434,"version":"4.8.0"},"reference-count":33,"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","award":["VX19-445-107"],"award-info":[{"award-number":["VX19-445-107"]}],"id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"crossref","award":["VX19-445-107"],"award-info":[{"award-number":["VX19-445-107"]}],"id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"crossref"}]}],"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>A 24-week, phase 3, open-label study showed elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) was safe and efficacious in children aged 6\u201311\u2009years with cystic fibrosis (CF) and one or more F508del-CFTR alleles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess long-term safety and efficacy of ELX\/TEZ\/IVA in children who completed the pivotal 24-week phase 3 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this phase 3, two-part (part A and part B), open-label extension study, children aged \u22656\u2009years with CF heterozygous for F508del and a minimal function CFTR mutation (F\/MF genotypes) or homozygous for F508del (F\/F genotype) who completed the 24-week parent study received ELX\/TEZ\/IVA based on weight. Children weighing &amp;lt;30\u2009kg received ELX 100\u2009mg once daily\/TEZ 50\u2009mg once daily\/IVA 75\u2009mg every 12\u2009hours, whereas children weighing \u226530\u2009kg received ELX 200\u2009mg once daily\/TEZ 100\u2009mg once daily\/IVA 150\u2009mg every 12\u2009hours (adult dose). The 96-week analysis of part A of this extension study is reported here.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Sixty-four children (F\/MF genotypes, n\u2009=\u200936; F\/F genotype, n\u2009=\u200928) were enrolled and received one or more doses of ELX\/TEZ\/IVA. Mean (SD) period of exposure to ELX\/TEZ\/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride concentration decreased (\u221262.3 [95% CI, \u221265.9 to \u221258.8] mmol\/L), Cystic Fibrosis Questionnaire-Revised respiratory domain score increased (13.3 [95% CI, 11.4 to 15.1] points), and lung clearance index 2.5 decreased (\u22122.00 [95% CI, \u22122.45 to \u22121.55] units). Increases in growth parameters were also observed. The estimated pulmonary exacerbation rate per 48\u2009weeks was 0.04. The annualized rate of change in percent predicted FEV1 was 0.51 (95% CI, \u22120.73 to 1.75) percentage points per year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ELX\/TEZ\/IVA continued to be generally safe and well tolerated in children aged \u22656\u2009years through an additional 96\u2009weeks of treatment. Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX\/TEZ\/IVA in this pediatric population.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT04183790).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202301-0021oc","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T09:22:50Z","timestamp":1683537770000},"page":"68-78","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":75,"title":["Long-Term Safety and Efficacy of Elexacaftor\/Tezacaftor\/Ivacaftor in Children Aged \u22656 Years with Cystic Fibrosis and at Least One\n                    <i>F508del<\/i>\n                    Allele: A Phase 3, Open-Label Clinical Trial"],"prefix":"10.1093","volume":"208","author":[{"given":"Claire","family":"Wainwright","sequence":"first","affiliation":[{"name":"Queensland Children\u2019s Hospital, South Brisbane, Queensland, Australia"},{"name":"Child Health Research Centre, University of Queensland, South Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna A.","family":"McColley","sequence":"additional","affiliation":[{"name":"Ann & Robert H. 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