Cystic FibrosisPhase 3NCT03525574
A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
A Phase 3 study testing ELX/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 110 sites in 13 countries.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- ELX/TEZ/IVA and IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 507 participants
- Where
- 110 sitesin 13 countries
- Study dates
- 9 Oct 2018to 9 Jan 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
110 sites in 13 countries.
110 sites in 13 countries
United States52 sites
Akron Children's Hospital
Akron, Ohio, 44308
UNM Clinical and Translational Science Center
Albuquerque, New Mexico, 87131
Children's Specialty Services at North Druid Hills
Atlanta, Georgia, 30324
Augusta University
Augusta, Georgia, 30912
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Billings Clinic Hospital
Billings, Montana, 59101
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
Boston, Massachusetts, 02114
UNC Marsico Clinical Research Center
Chapel Hill, North Carolina, 27517
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Primary Care Center
Charlottesville, Virginia, 22908
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Northwestern Memorial Hospital
Chicago, Illinois, 60611
UC Health Holmes
Cincinnati, Ohio, 45220
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Vermont Lung Center
Colchester, Vermont, 05446
Nationwide Children's Hospital
Columbus, Ohio, 43205
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Dayton Children's Hospital
Dayton, Ohio, 45404
National Jewish Health
Denver, Colorado, 80206
Harper University Hospital
Detroit, Michigan, 48201
University of Florida, Shands Hospital
Gainesville, Florida, 32610
Joe DiMaggio Cystic Fibrosis & Pulmonary Center
Hollywood, Florida, 33021
Nemours Children's Specialty Care
Jacksonville, Florida, 32207
The University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Miller Children's Hospital / Long Beach Memorial
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792
CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
West Virginia University
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
Tulane Medical Center
New Orleans, Louisiana, 70112
The Cystic Fibrosis Center, Mount Sinai Beth Israel
New York, New York, 10003
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
Kaiser Permanente
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Nebraska Medical Center
Omaha, Nebraska, 68198
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803
Nemours Children's Hospital
Orlando, Florida, 32827
Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Maine Medical Partners
Portland, Maine, 04102
Children's Hospital of Richmond at VCU, Children's Pavilion
Richmond, Virginia, 23298
University of California Davis Medical Center
Sacramento, California, 95817
UCSF Gateway Medical Center
San Francisco, California, 94143
University of Washington Medical Center
Seattle, Washington, 98195
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606
ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
Toledo, Ohio, 43606
Banner University of Arizona Medical Center
Tucson, Arizona, 85724
New York Medical College
Valhalla, New York, 10595
United Kingdom8 sites
Belfast City Hospital
Belfast
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
Birmingham
Western General Hospital
Edinburgh
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter
Leeds General Infirmary
Leeds
King's College Hospital
London
Royal Manchester Children's Hospital
Manchester
Southampton General Hospital
Southampton
France7 sites
Centre Hospitalier Lyon Sud
Benite Cedex
Groupe Hospitaler Pellegrin, CHU De Bordeaux
Bordeaux
CHU Marseille - Hopital Nord
Marseille
CHU de Nice - Hopital Pasteur
Nice
Hopital Cochin
Paris
CHU de Rouen - Hopital Charles Nicolle
Rouen
Hopital Foch (Suresnes), Hopital Foch, Adultes
Suresnes
Germany7 sites
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
Erlangen
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
Giessen
Hannover Medical School
Hanover
Johannes Gutenberg-Universitaet
Mainz
Dr. von Haunersches Kinderspital
München
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Tübingen
University Hospital Wuerzburg
Würzburg
Italy7 sites
Azienda Ospedaliero Universitaria Ospendali Riuniti
Ancona
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
Florence
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
Genova
Azienda Ospedaliera Universitaria Policlinico G. Martino
Messina
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
Potenza
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
Verona
Canada6 sites
University of Calgary Medical Clinic of the Foothills Medical Centre
Calgary
McGill University Health Centre, Glen Site, Montreal Children's Hospital
Montreal
Centre Hospitalier De L'Universite Laval
Québec
The Hospital for Sick Children
Toronto
British Columbia's Children's Hospital
Vancouver
St. Paul's Hospital
Vancouver
Australia5 sites
Women & Children's Hospital
North Adelaide
The Royal Children's Hospital
Parkville
Mater Misericordiae Ltd
South Brisbane
The Children's Hospital at Westmead
Westmead
Westmead Hospital
Westmead
Belgium5 sites
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels
Universitair Ziekenhuis Brussel - Campus Jette
Brussels
UZ Antwerpen
Edegem
Universitair Ziekenhuis Gent
Ghent
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
Netherlands5 sites
Academic Medical Center
Amsterdam
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan
UMC St. Radboud
Nijmegen
Erasmus Medical Center
Rotterdam
HagaZiekenhuis van den Haag
The Hague
Austria4 sites
University of Graz
Graz
Medizinische Universität Innsbruck
Innsbruck
LKH - Universitätsklinikum der PMU Salzburg
Salzburg
Medizinische Universitat Wien
Vienna
Greece1 site
General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
Marousi
About this study
Official title: 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
- Conditions
- Cystic Fibrosis
- Being tested
- ELX/TEZ/IVA, IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELX/TEZ/IVADrug
Also called VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor
Fixed-dose combination (FDC) tablet for oral administration.
IVADrug
Also called VX-770, ivacaftor
Tablet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| ELX/TEZ/IVA | Experimental | 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. Receives: Drug: ELX/TEZ/IVA; Drug: IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 up to Week 196
Secondary outcomes (16)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline at Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2018
- Study start9 Oct 2018
- Primary completion9 Jan 2023
- Study completion9 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 507 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525574
- Sponsor's protocol ID
- VX17-445-105
- Other IDs
- 2018-000185-11, 2018
- Status last verified
- Sep 2025
- First submitted
- 2 May 2018
- Last updated
- 24 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
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 Oct;211(10):1901-1914. doi: 10.1164/rccm.202411-2231OC.
PubMed 40209082Heneghan 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.
PubMed 37983082Southern 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.
PubMed 33331662