Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

The New England Journal of Medicine
Steven M RoweJane C Davies

Abstract

Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene that lead to progressive respiratory decline. Some mutant CFTR proteins show residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone does not restore activity to Phe508del mutant CFTR. We conducted a randomized, double-blind, placebo-controlled, phase 3, crossover trial to evaluate the efficacy and safety of ivacaftor alone or in combination with tezacaftor, a CFTR corrector, in 248 patients 12 years of age or older who had cystic fibrosis and were heterozygous for the Phe508del mutation and a CFTR mutation associated with residual CFTR function. Patients were randomly assigned to one of six sequences, each involving two 8-week intervention periods separated by an 8-week washout period. They received tezacaftor-ivacaftor, ivacaftor monotherapy, or placebo. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from the baseline value to the average of the week 4 and week 8 measurements in each intervention period. The number of analyzed intervention periods was 162 for tezacaftor-ivacaftor, 157 for ivacaftor alone, and 162 for placebo. ...Continue Reading

References

Feb 1, 1993·Pediatric Pulmonology·X WangB G Ferris
Jan 5, 1999·American Journal of Respiratory and Critical Care Medicine·J L HankinsonK B Fedan
Dec 14, 2004·American Journal of Respiratory and Critical Care Medicine·David M RodmanJerry A Nick
Jul 15, 2006·American Journal of Respiratory and Critical Care Medicine·Michael WilschanskiPeter Durie
Jul 27, 2007·Proceedings of the American Thoracic Society·Christopher H Goss, Alexandra L Quittner
May 6, 2008·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·C CastellaniJ S Elborn
May 1, 2009·Lancet·Brian P O'Sullivan, Steven D Freedman
Sep 8, 2009·QJM : Monthly Journal of the Association of Physicians·D M ComerJ S Elborn
Nov 19, 2010·The New England Journal of Medicine·Frank J AccursoBonnie W Ramsey
Oct 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Fredrick Van GoorPaul A Negulescu
Nov 4, 2011·The New England Journal of Medicine·Bonnie W RamseyUNKNOWN VX08-770-102 Study Group
Jun 23, 2012·American Journal of Respiratory and Critical Care Medicine·John P Clancy, Manu Jain
Jul 31, 2013·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Fredrick Van GoorBeth J Hoffman
May 20, 2015·The New England Journal of Medicine·Claire E WainwrightUNKNOWN TRANSPORT Study Group
Jun 14, 2015·The Lancet. Respiratory Medicine·Richard B MossUNKNOWN VX11-770-110 (KONDUCT) Study Group
May 4, 2016·Lancet·J Stuart Elborn
Nov 3, 2016·American Journal of Respiratory and Critical Care Medicine·Carlos E MillaUNKNOWN VX13-809-011 Part B Investigator Group *
Nov 4, 2017·The New England Journal of Medicine·Jennifer L Taylor-CousarJ Stuart Elborn

❮ Previous
Next ❯

Citations

Apr 17, 2018·Pediatric Pulmonology·Stacey L MartinianoElisabeth P Dellon
Mar 15, 2018·Current Opinion in Pediatrics·Elizabeth B Burgener, Richard B Moss
Feb 23, 2018·JCI Insight·John J BrewingtonJohn P Clancy
Dec 22, 2017·Expert Opinion on Emerging Drugs·Kristin M Hudock, John Paul Clancy
Jan 13, 2018·American Journal of Respiratory and Critical Care Medicine·Simon Y GraeberBurkhard Tümmler
Jun 2, 2018·Expert Review of Respiratory Medicine·Natalie E West, Patrick A Flume
Jun 22, 2018·Pediatric Pulmonology·Adrienne P Savant, Susanna A McColley
Aug 3, 2018·The Cochrane Database of Systematic Reviews·Kevin W SouthernSarah J Nevitt
Aug 4, 2018·Expert Review of Respiratory Medicine·Marc A Sala, Manu Jain
May 2, 2018·Annual Review of Genomics and Human Genetics·Wanda K O'Neal, Michael R Knowles
Sep 1, 2018·Annual Review of Genomics and Human Genetics·Amanda KrauseMichèle Ramsay
Aug 22, 2018·Expert Review of Respiratory Medicine·Oliver J McElvaneyNoel G McElvaney
Oct 6, 2018·Pediatric Pulmonology·John P Clancy
Nov 24, 2018·Respirology : Official Journal of the Asian Pacific Society of Respirology·Catherine Rang, John Wilson
Dec 19, 2018·Pediatric Pulmonology·Donatello SalvatoreFabio Majo
Dec 27, 2018·The New England Journal of Medicine·James E MojicaLida P Hariri
Jan 30, 2019·Clinical and Translational Science·Varun GargJulie Lekstrom-Himes
Feb 15, 2019·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Marianne SkovTacjana Pressler
Jan 12, 2019·BMJ : British Medical Journal·Leonard E Riley, Anupa P Nadkarni
Feb 15, 2019·Minerva pediatrica·Valeria R VillellaLuigi Maiuri
May 21, 2019·Pediatric Pulmonology·Adrienne P Savant, Susanna A McColley
Sep 11, 2019·Current Opinion in Pulmonary Medicine·Renske van der MeerHarry G M Heijerman
Nov 13, 2019·Pediatric Pulmonology·Disha JoshiEric J Sorscher
Oct 19, 2019·Expert Review of Respiratory Medicine·Sarah L PatersonAlexander R Horsley
Jan 22, 2020·The Journal of Clinical Investigation·Guadalupe Ortiz-MuñozMark R Looney
Dec 21, 2019·American Journal of Respiratory and Critical Care Medicine·Marcus A MallSteven M Rowe
May 27, 2020·Pediatric Pulmonology·Nazan ÇobanoğluDeniz Doğru
Aug 23, 2020·Journal of Clinical Medicine·Jennifer L Taylor-Cousar
Oct 20, 2018·The New England Journal of Medicine·Dominic KeatingUNKNOWN VX16-445-001 Study Group
Apr 24, 2019·Pediatric Pulmonology·Sachinkumar B SinghAnthony J Fischer
May 16, 2019·Pediatric Pulmonology·Stacey L MartinianoEdith T Zemanick
Jul 1, 2020·Laryngoscope Investigative Otolaryngology·Brian Jake JohnsonErin K O'Brien
Aug 8, 2020·Der Radiologe·Mirjam Stahl
Nov 4, 2017·The New England Journal of Medicine·Hartmut Grasemann
Dec 26, 2018·Frontiers in Pharmacology·Nikhil T AwatadeShafagh A Waters
Nov 28, 2018·Molecular Diagnosis & Therapy·Giulio Cabrini
Mar 16, 2019·Frontiers in Pharmacology·Iwona PrankeIsabelle Sermet-Gaudelus
Jul 20, 2019·Science·Candela ManfrediEric J Sorscher

❮ Previous
Next ❯

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