Trial reportThe New England journal of medicine2018
VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 409 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
409citing papers in PubMed, 4 pooled it
59.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Effect of the CFTR-modulating Triple Therapy Elexacaftor - Tezacaftor - Ivacaftor on Numerical Distribution in Peripheral Mononuclear Immune Cells Derived From Patients With Cystic Fibrosis
Who cites it
409 citing papers in PubMed, 4 syntheses or guidelines pooled it, 717 citations in OpenAlex.
- Effect of CFTR modulators on glucose homeostasis in children and young adults with cystic fibrosis-related diabetes: a systematic review.Frontiers in endocrinology · 2025Pooled it
- Clinimetric properties of field exercise tests in cystic fibrosis: a systematic review.European respiratory review : an official journal of the European Respiratory Society · 2024Pooled it
- Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2024Pooled it
- Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).The Cochrane database of systematic reviews · 2023Pooled it
- Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least oneThe European respiratory journal · 2023Trial
- Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials.The Lancet. Respiratory medicine · 2023Trial
- Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.The Lancet. Respiratory medicine · 2023Trial
- Article
- Principles of ribosome-associated protein quality control during the synthesis of CFTR.The EMBO journal · 2026Article
- Combining Gene Therapy with Current Modulator Treatments for Cystic Fibrosis: A Promising Area of Research.Pharmaceutics · 2026Review
- Impact of Elexacaftor/Tezacaftor/Ivacaftor on Systemic Antibiotic Utilization in Pediatric Patients With Cystic Fibrosis.Pediatric pulmonology · 2026Article
- Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features.International journal of molecular sciences · 2026Review
- A cell-permeable nanobody to restore F508del cystic fibrosis transmembrane conductance regulator activity.Nature chemical biology · 2026Article
- Alveolar macrophage subtypes express cholesterol and inflammation genes in cystic fibrosis.Life science alliance · 2026Article
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Prenatal CFTR modulator therapy for fetal cystic fibrosis: Emerging evidence, clinical considerations, and future directions.Pregnancy (Hoboken, N.J.) · 2026Review
- Evolving Cystic Fibrosis Therapy: The Good, the Sad, and the Hopeful.Children (Basel, Switzerland) · 2026Review
- Review
- Toward Precision Electrochemical Sensing of CFTR Function in Cystic Fibrosis Models.Analytical chemistry · 2026Article
- Clinical Outcomes in Concurrent Cohorts of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA)-Treated versus ELX/TEZ/IVA-Ineligible Individuals with Cystic Fibrosis in the US during COVID-19.Pulmonary therapy · 2026Article
349 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
21 authors at 12 institutions in 4 countries.
Dominic KeatingFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Gautham MarigowdaFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Lucy BurrFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Cori DainesFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Marcus A MallFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Edward F McKoneFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Bonnie W RamseyFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Steven M RoweFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Laura A SassFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Elizabeth TullisFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Charlotte M McKeeFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Samuel M MoskowitzFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Sarah RobertsonFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Jessica SavageFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Christopher SimardFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Fredrick Van GoorFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
David WaltzFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Fengjuan XuanFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Tim YoungFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
Jennifer L Taylor-CousarFrom Alfred Hospital, Melbourne, VIC (D.K.), and Mater Hospital, Brisbane, QLD (L.B.) - both in Australia; Vertex Pharmaceuticals, Boston (G.M., C.M.M., S.M.M., S.R., J.S., C.S., F.V.G., D.W., F.X., T.Y.); Banner University Medical Center, Tucson, AZ (C.D.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - both in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.); Seattle Children's Hospital, Seattle (B.W.R.); University of Alabama at Birmingham, Birmingham (S.M.R.); Children's Hospital of the King's Daughters, Norfolk, VA (L.A.S.); St. Michael's Hospital, Toronto (E.T.); and National Jewish Health, Denver (J.L.T.-C.).
VX16-445-001 Study Group
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · DEVertex Pharmaceuticals (United States) · USBanner - University Medical Center Tucson · USChildren's Hospital of The King's Daughters · USGerman Center for Lung Research · DEMater Adult Hospital · AUSeattle Children's Hospital · USSt Michael’s Hospital · IEThe Alfred Hospital · AUUniversity College Dublin · IEUniversity of Alabama at Birmingham · USUniversity of Colorado Denver · US
Funding
UAB Center for Clinical and Translational Science (CCTS)UL1TR001417 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2015 to 2018
$31.4MUAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Brian R. Davis · 2007 to 2026
$23.0MTranslational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI Christopher Hooper Goss · 2010 to 2026
$21.4MThe University of Iowa Clinical and Translational Science AwardU54TR001356 · NCATS · UNIVERSITY OF IOWA · PI WINOKUR, PATRICIA · 2015 to 2016
$7.1MTranslational Program in CFTR-Related Airway DiseasesR35HL135816 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2017 to 2022
$6.3MNCATS NIH HHS U54 TR001356NCATS NIH HHS UL1 TR001417NHLBI NIH HHS R35 HL135816NIDDK NIH HHS P30 DK072482NIDDK NIH HHS P30 DK089507
Abstract
backgroundVX-445 is a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector designed to restore Phe508del CFTR protein function in patients with cystic fibrosis when administered with tezacaftor and ivacaftor (VX-445-tezacaftor-ivacaftor).
methodsWe evaluated the effects of VX-445-tezacaftor-ivacaftor on Phe508del CFTR protein processing, trafficking, and chloride transport in human bronchial epithelial cells. On the basis of in vitro activity, a randomized, placebo-controlled, double-blind, dose-ranging, phase 2 trial was conducted to evaluate oral VX-445-tezacaftor-ivacaftor in patients heterozygous for the Phe508del CFTR mutation and a minimal-function mutation (Phe508del-MF) and in patients homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del) after tezacaftor-ivacaftor run-in. Primary end points were safety and absolute change in percentage of predicted forced expiratory volume in 1 second (FEV
resultsIn vitro, VX-445-tezacaftor-ivacaftor significantly improved Phe508del CFTR protein processing, trafficking, and chloride transport to a greater extent than any two of these agents in dual combination. In patients with cystic fibrosis, VX-445-tezacaftor-ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. The treatment also resulted in an increased percentage of predicted FEV
conclusionsThe use of VX-445-tezacaftor-ivacaftor to target Phe508del CFTR protein resulted in increased CFTR function in vitro and translated to improvements in patients with cystic fibrosis with one or two Phe508del alleles. This approach has the potential to treat the underlying cause of cystic fibrosis in approximately 90% of patients. (Funded by Vertex Pharmaceuticals; VX16-445-001 ClinicalTrials.gov number, NCT03227471 ; and EudraCT number, 2017-000797-11 .).
Indexed as
AdolescentAdultAllelesAminophenolsBenzodioxolesChloride Channel AgonistsChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDouble-Blind MethodDrug CombinationsFemaleForced Expiratory VolumeGenotypeHumansIndolesAminophenolsBenzodioxolesCFTR protein, humanChloride Channel AgonistsChloridesCystic Fibrosis Transmembrane Conductance RegulatorDrug CombinationselexacaftorIndolesivacaftorPyrazolesPyridinesPyrrolidinesQuinolonestezacaftor
Identifiers
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Registered trials
NCT03227471ClinicalTrials.gov
NCT05576324ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.