Trial reportThe New England journal of medicine2018
VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.
2 registry-linked trialsAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
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 160 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis
A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
Who cites it
160 citing papers in PubMed, 6 syntheses or guidelines pooled 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
- Efficacy and Safety of Triple Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Patients With Cystic Fibrosis: A Meta-Analysis of Randomized Controlled Trials.Frontiers in pharmacology · 2022Pooled 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 · 2020Pooled it
- From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis.International journal of molecular sciences · 2020Pooled it
- Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.The New England journal of medicine · 2019Trial
- VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles.The New England journal of medicine · 2018Trial
- Article
- Alveolar macrophage subtypes express cholesterol and inflammation genes in cystic fibrosis.Life science alliance · 2026Article
- Review
- Short-term monitoring of CFTR modulator therapy in adults and children with cystic fibrosis using low and ultra-low-dose lung CT.La Radiologia medica · 2026Article
- Genetic and chemical correction of cystic fibrosis reduces airway susceptibility to SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism.Nature communications · 2025Article
- Photoaffinity Ligand of Cystic Fibrosis Corrector VX-445 Identifies SCCPDH as an Off-Target.ACS chemical biology · 2025Article
- The potentiator ivacaftor is essential for pharmacological restoration of F508del-CFTR function and mucociliary clearance in cystic fibrosis.JCI insight · 2025Article
- Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication.International journal of molecular sciences · 2025Review
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Toward in vivo bronchoscopic functional CFTR assessment using a short circuit current measurement probe.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors.
Jane C DaviesFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Samuel M MoskowitzFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Cynthia BrownFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Alexander HorsleyFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Marcus A MallFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Edward F McKoneFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Barry J PlantFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Dario PraisFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Bonnie W RamseyFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Jennifer L Taylor-CousarFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Elizabeth TullisFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Ahmet UluerFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Charlotte M McKeeFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Sarah RobertsonFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Rebecca A ShillingFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Christopher SimardFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Fredrick Van GoorFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
David WaltzFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Fengjuan XuanFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Tim YoungFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
Steven M RoweFrom Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.), and the Manchester Adult Cystic Fibrosis Centre, Manchester (A.H.) - both in the United Kingdom; Vertex Pharmaceuticals (S.M.M., C.M.M., S.R., R.A.S., C.S., F.V.G., D.W., F.X., T.Y.) and Boston Children's Hospital and Brigham and Women's Hospital (A.U.) - all in Boston; Indiana University School of Medicine, Indianapolis (C.B.); Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, and the German Center for Lung Research, Giessen - all in Germany (M.A.M.); St. Vincent's University Hospital and University College Dublin School of Medicine, Dublin (E.F.M.), and Cork University Hospital and University College Cork, Cork (B.J.P.) - all in Ireland; Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.P.) - both in Israel; Seattle Children's Hospital, Seattle (B.W.R.); National Jewish Health, Denver (J.L.T.-C.); St. Michael's Hospital, Toronto (E.T.); and the University of Alabama at Birmingham, Birmingham (S.M.R.).
VX16-659-101 Study Group
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
backgroundThe next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659-tezacaftor-ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis.
methodsWe evaluated the effects of VX-659-tezacaftor-ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659-tezacaftor-ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del-MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del-Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV
resultsVX-659-tezacaftor-ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659-tezacaftor-ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659-tezacaftor-ivacaftor resulted in significant mean increases in the percentage of predicted FEV
conclusionsRobust in vitro activity of VX-659-tezacaftor-ivacaftor targeting Phe508del CFTR protein translated into improvements for patients with Phe508del-MF or Phe508del-Phe508del genotypes. VX-659 triple-combination regimens have the potential to treat the underlying cause of disease in approximately 90% of patients with cystic fibrosis. (Funded by Vertex Pharmaceuticals; VX16-659-101 and VX16-659-001 ClinicalTrials.gov numbers, NCT03224351 and NCT03029455 .).
Indexed as
AdolescentAdultAllelesAminophenolsBenzodioxolesCells, CulturedChloride Channel AgonistsChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDouble-Blind MethodDrug CombinationsFemaleForced Expiratory VolumeGenotypeHumansAminophenolsBenzodioxolesCFTR protein, humanChloride Channel AgonistsChloridesCystic Fibrosis Transmembrane Conductance RegulatorDrug CombinationsIndolesivacaftorPyrazolesPyrrolidinesQuinolonestezacaftorVX-659
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What OpenQuestion holds
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Read underepoch 390
Registered trials
NCT03029455ClinicalTrials.gov
NCT03224351ClinicalTrials.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.