A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation

The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IVA; Drug: ELX/TEZ/IVA

• Study Type: Interventional
• Enrollment (Actual): 507
• Phase: Phase 3

Expanded Access

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Contacts and Locations

Study Locations

• Australia
  • North Adelaide, Australia
    • Women & Children's Hospital
  • Parkville, Australia
    • The Royal Children's Hospital
  • South Brisbane, Australia
    • Mater Misericordiae Ltd
  • Westmead, Australia
    • The Children's Hospital at Westmead
  • Westmead, Australia
    • Westmead Hospital
• Austria
  • Graz, Austria
    • University of Graz
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck
  • Salzburg, Austria
    • LKH - Universitätsklinikum der PMU Salzburg
  • Vienna, Austria
    • Medizinische Universität Wien
• Belgium
  • Brussels, Belgium
    • Universitair Ziekenhuis Brussel - Campus Jette
  • Brussels, Belgium
    • Cliniques universitaires de Bruxelles Hopital Erasme
  • Edegem, Belgium
    • UZ Antwerpen
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
• Canada
  • Calgary, Canada
    • University of Calgary Medical Clinic of the Foothills Medical Centre
  • Montreal, Canada
    • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Québec, Canada
    • Centre Hospitalier de l'Université Laval
  • Toronto, Canada
    • The Hospital for Sick Children
  • Vancouver, Canada
    • British Columbia's Children's Hospital
  • Vancouver, Canada
    • St. Paul's Hospital
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice Brno
  • Prague, Czechia
    • Fakultni nemocnice v Motole
• France
  • Benite Cedex, France
    • Centre Hospitalier Lyon Sud
  • Bordeaux, France
    • Groupe Hospitaler Pellegrin, CHU De Bordeaux
  • Marseille, France
    • Chu Marseille - Hopital Nord
  • Nice, France
    • CHU de Nice - Hopital Pasteur
  • Paris, France
    • Hôpital Cochin
  • Rouen, France
    • CHU de Rouen - Hôpital Charles Nicolle
  • Suresnes, France
    • Hopital Foch (Suresnes), Hopital Foch, Adultes
• Germany
  • Erlangen, Germany
    • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
  • Giessen, Germany
    • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
  • Hanover, Germany
    • Hannover Medical School
  • Mainz, Germany
    • Johannes Gutenberg-Universitaet
  • München, Germany
    • Dr. von Haunersches Kinderspital
  • Tübingen, Germany
    • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
  • Würzburg, Germany
    • University Hospital Wuerzburg
• Greece
  • Marousi, Greece
    • General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria Ospendali Riuniti
  • Florence, Italy
    • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
  • Genova, Italy
    • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
  • Messina, Italy
    • Azienda Ospedaliera Universitaria Policlinico G. Martino
  • Milan, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Potenza, Italy
    • Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
  • Verona, Italy
    • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Heidelberglaan, Netherlands
    • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
  • Nijmegen, Netherlands
    • UMC St. Radboud
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • The Hague, Netherlands
    • HagaZiekenhuis van Den Haag
• Sweden
  • Stockholm, Sweden
    • Karolinska Universitetssjukhuset, Huddinge
• United Kingdom
  • Belfast, United Kingdom
    • Belfast City Hospital
  • Birmingham, United Kingdom
    • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
  • Edinburgh, United Kingdom
    • Western General Hospital
  • Exeter, United Kingdom
    • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • King's College Hospital
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital / Long Beach Memorial
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Madera, California, United States, 93636
      • Valley Children's Hospital
    • Oakland, California, United States, 94611
      • Kaiser Permanente
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94143
      • UCSF Gateway Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida, Shands Hospital
    • Hollywood, Florida, United States, 33021
      • Joe DiMaggio Cystic Fibrosis & Pulmonary Center
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Specialty Care
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital Cardiac and Lung Transplant Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Children's Specialty Services at North Druid Hills
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Ann & Robert Lurie Children's Hospital of Chicago
    • Peoria, Illinois, United States, 61637
      • Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Partners
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • UNM Clinical and Translational Science Center
  • New York
    • New York, New York, United States, 10003
      • The Cystic Fibrosis Center, Mount Sinai Beth Israel
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • UNC Marsico Clinical Research Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45220
      • UC Health Holmes
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Primary Care Center
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU, Children's Pavilion
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospitals and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.

Exclusion Criteria:

• History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.
• Current participation in an investigational drug trial (other than a parent study)

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ELX/TEZ/IVA; Treatment Period: Participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hrs (q12h) in the treatment period for 192 weeks. Extension Period: Participants from certain countries participated in extension period and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: ELX/TEZ/IVA; Fixed-dose combination (FDC) tablet for oral administration.; Other Names: VX-445/VX-661/VX-770; elexacaftor/tezacaftor/ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From Day 1 up to Week 196

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set	Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set	Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Time to First PEx for 102/105 Efficacy Set	Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Time to First PEx for 103/105 Efficacy Set	Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in BMI Z-score for 102/105 Efficacy Set	BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in BMI Z-score for 103/105 Efficacy Set	BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Body Weight for 102/105 Efficacy Set	This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change in Body Weight for 103/105 Efficacy Set	This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.	From Baseline at Week 192

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
• Daines CL, Polineni D, Tullis E, Costa S, Linnemann RW, Mall MA, McKone EF, Quon BS, Ringshausen FC, Selvadurai H, Taylor-Cousar JL, Withers NJ, Sawicki GS, Lee T, Ahluwalia N, Morlando Geiger J, Jennings M, Tan YV, Waltz D, Ramsey B, Griese M; VX17-445-105 Study Group. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Extension Study. Am J Respir Crit Care Med. 2025 Apr 10. doi: 10.1164/rccm.202411-2231OC. Online ahead of print.
• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2018
• Primary Completion (Actual): January 9, 2023
• Study Completion (Actual): January 9, 2023

Study Registration Dates

• First Submitted: May 2, 2018
• First Submitted That Met QC Criteria: May 2, 2018
• First Posted (Actual): May 15, 2018

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; elexacaftor, ivacaftor, tezacaftor drug combination; ivacaftor
• Other Study ID Numbers: VX17-445-105; 2018-000185-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No