A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive CFTR Mutation and No F508del Mutation
2 other identifiers
interventional
597
19 countries
165
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no F508del mutation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2021
165 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 29, 2021
CompletedFirst Posted
Study publicly available on registry
October 13, 2021
CompletedStudy Start
First participant enrolled
October 27, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 18, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2023
CompletedResults Posted
Study results publicly available
June 13, 2024
CompletedJune 13, 2024
May 1, 2024
1.6 years
September 29, 2021
May 16, 2024
May 16, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Week 24
Secondary Outcomes (3)
Absolute Change in Sweat Chloride (SwCl)
From Baseline Through Week 24
Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)
From Baseline Through Week 24
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)
From Baseline Through Week 24
Study Arms (2)
ELX/TEZ/IVA
ACTIVE COMPARATORFollowing elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
VX-121/TEZ/D-IVA
EXPERIMENTALFollowing ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Interventions
Fixed-dose combination tablets for oral administration.
Fixed-dose combination tablets for oral administration.
Placebo matched to VX-121/TEZ/D-IVA for oral administration.
Placebo matched to ELX/TEZ/IVA for oral administration.
Eligibility Criteria
You may qualify if:
- Participant has one of the following genotypes:
- Homozygous for F508del;
- Heterozygous for F508del and a gating (F/G) mutation;
- Heterozygous for F508del and a residual function (F/RF) mutation;
- At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA and no F508del mutation
- Forced expiratory volume in 1 second (FEV1) value \>=40% and \<=90% of predicted mean for age, sex, and height for participants currently receiving CFTR protein modulator therapy; FEV1 \>=40% and \<=80% for participants not currently receiving CFTR protein modulator therapy
You may not qualify if:
- History of solid organ or hematological transplantation
- Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Pregnant or breast-feeding females
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (170)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner University of Arizona Medical Center
Tucson, Arizona, 85724, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
Children's Hospital of Colorado
Aurora, Colorado, 80045, United States
National Jewish Health
Denver, Colorado, 80206, United States
Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
Nemours Children's Specialty Care
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine
Miami, Florida, 33136, United States
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803, United States
Nemours Children's Specialty Care, Pensacola
Pensacola, Florida, 32514, United States
Johns Hopkins All Children's Hospital Outpatient Care Center
St. Petersburg, Florida, 33701, United States
The Emory Clinic at Chantilly
Atlanta, Georgia, 30324, United States
St. Luke's Cystic Fibrosis Center of Idaho
Boise, Idaho, 83702, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
Maine Medical Partners
Portland, Maine, 04102, United States
Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
Boston, Massachusetts, 02114, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
UMass Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Michigan Medicine
Ann Arbor, Michigan, 48109-5212, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
Grand Rapids, Michigan, 49546, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
The Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Billings Clinic
Billings, Montana, 59101, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
CF Therapeutics Development Center of Western New York
Buffalo, New York, 14203, United States
Northwell Health- Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
Columbia University Medical Center
New York, New York, 10032, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27104, United States
Akron Children's Hospital
Akron, Ohio, 44308, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, 73112, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Prisma Health Richland Campus
Columbia, South Carolina, 29203, United States
Sanford Children's Speciality Clinic
Sioux Falls, South Dakota, 57105, United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8558, United States
Cook Children's Health Care System
Fort Worth, Texas, 76104, United States
University of Utah - Primary Children's Medical Center
Salt Lake City, Utah, 84132, United States
Vermont Lung Center
Colchester, Vermont, 05446, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
Spokane, Washington, 99204, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
University Hospital and UW Health Clinics
Madison, Wisconsin, 53792, United States
Royal Prince Alfred Hospital
Camperdown, Australia
The Prince Charles Hospital
Chermside, Australia
Alfred Hospital
Melbourne, VIC, Australia
Institute for Respiratory Health
Nedlands, Australia
Telethon Kids Institute
Nedlands, Australia
The Royal Children's Hospital
Parkville, VIC, Australia
Sydney Children's Hospital
Randwick, Australia
Mater Adult Hospital
South Brisbane, Australia
Queensland Children's Hospital
South Brisbane, Australia
Westmead Hospital
Westmead, Australia
University of Graz
Graz, Austria
Medizinische Universität Innsbruck
Innsbruck, Austria
Uniklinikum Salzburg - Universitätsklinik für Pneumologie/Lungenheilkunde
Salzburg, Austria
Medizinische Universität Wien
Vienna, Austria
Abteilung fuer Pulmologie Klinikum Wels-Grieskirchen
Wels, Austria
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, Belgium
Universitair Ziekenhuis Brussel - Campus Jette
Brussels, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, Belgium
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Belgium
University of Calgary Medical Clinic of the Foothills Medical Centre
Calgary, Canada
Stollery Children's Hospital
Edmonton, Canada
St. Joseph's Health Care London
London, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
Montreal, Canada
McGill University Health Centre, Glen Site, Montreal Children's Hospital
Montreal, Canada
Institut Universitaire de Cardiologie et Pneumologie de Quebec - Universite Laval
Québec, Canada
St. Michael's Hospital
Toronto, Canada
British Columbia Children's Hospital
Vancouver, Canada
St. Paul's Hospital
Vancouver, Canada
Aarhus University Hospital
Aarhus, Denmark
Juliane Marie Center, Rigshospitalet
Copenhagen, Denmark
Groupe Hospitaler Pellegrin, CHU De Bordeaux
Bordeaux, France
CHU Lyon - Hopital Femme Mere-Enfant
Bron, France
Centre Hospitalier Intercommunal Creteil
Créteil, France
Institut Cœur Poumon, CHU de Lille
Lille, France
Hopital Arnaud de Villeneuve
Montpellier, France
Centre Hospitalier Universitaire De Nantes - G. R. Laennec
Nantes, France
Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur
Nice, France
Hopital Cochin
Paris, France
Hopital Necker, Enfants Malades
Paris, France
Hopital Robert Debre
Paris, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Centre de Perharidy
Roscoff, France
CHU de Rouen - Hopital Charles Nicolle
Rouen Cedex, Seine Maritime, France
Hôpital de Hautepierre, AX5
Strasbourg, France
Hopital Foch (Suresnes), Hopital Foch, Adultes
Suresnes, France
Hopital Bretonneau
Tours, France
Centre hospitalier universitaire de Nancy, Hôpital de Braboi
Vandœuvre-lès-Nancy, France
Charite Paediatric Pulmonology Department
Berlin, Germany
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
Erlangen, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen, Germany
Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
Essen, Germany
Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
Giessen, Germany
Pneumologisches Studienzentrum Muenchen-West
München, Germany
General Hospital of Thessaloniki "Papanikolaou"
Pilea Chortiatis, Greece
General Hospital of Thessaloniki 'Hippokratio', 3rd Pediatrics Department of Aristotle University of Thessaloniki
Thessaloniki, Greece
National Koranyi Institute for TBC and Pulmonology
Budapest, Hungary
Pulmonology Institute Torokbalint
Törökbálint, Hungary
Cork University Hospital
Cork, Ireland
Children's Health Ireland at Crumlin
Dublin, Ireland
Children's Health Ireland at Tallaght
Dublin, Ireland
Children's University Hospital, Dublin
Dublin, Ireland
St. Vincent's University Hospital
Dublin, Ireland
University Hospital Limerick (Adults)
Limerick, Ireland
University Hospital Limerick (Pediatrics)
Limerick, Ireland
Hadassah Medical Organization
Jerusalem, Israel
Schneider Children's Medical Center of Israel
Petach Tikvah, Israel
Sheba Medical Center - The Edmond and Lili Safra Children's Hospital
Tel Litwinsky, Israel
Azienda Ospedaliero Universitaria Ospedale Riuniti
Ancona, Italy
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
Florence, Italy
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
Genova, Italy
Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
Milan, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy
Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica
Orbassano, Italy
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
Potenza, Italy
Azienda Ospedaliera di Verona - Ospedale Civile Maggiore
Verona, Italy
Academisch Medisch Centrum (Academic Medical Centre)
Amsterdam, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
HagaZiekenhuis van den Haag
The Hague, Netherlands
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Utrecht, Netherlands
Greenlane Clinical Centre
Auckland, New Zealand
Starship Children's Hospital
Auckland, New Zealand
Canterbury Respiratory Research Group
Christchurch Hospital, New Zealand
Waikato Hospital
Hamilton, New Zealand
Haukeland Universitetssjukehus (CF)
Bergen, Norway
Oslo University Hospital, Department of Paediatric Medicine
Oslo, Norway
Pediatric Hospital Polanki named of Maciej Płażyński
Gdansk, Poland
Institute of Tuberculosis and Lung Diseases
Rabka-Zdrój, Poland
Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
Łomianki, Poland
Sahlgrenska Universitetssjukhuset
Gothenburg, Sweden
Lund University Skanes Universitetssjukhus
Malmo, Sweden
Karolinska Universitetssjukhuset, Huddinge
Stockholm, Sweden
Lindenhofspital - Quartier Bleu
Bern, Switzerland
Réseau Hospitalier Neuchâtelois
Neuchâtel, Switzerland
Kinderspital Zuerich
Zurich, Switzerland
Birmingham Children's Hospital
Birmingham, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
Cambridge, United Kingdom
Clinical Research Facility, Queen Elizabeth University Hospital
Glasgow, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
St. James University Hospital
Leeds, United Kingdom
King's College Hospital
London, United Kingdom
Royal Brompton Hospital
London, United Kingdom
St. Bartholomew's Hospital
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
Penarth, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Related Publications (2)
Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, Kotsimbos T, Mermis J, Braun AT, O'Carroll M, Sutharsan S, Ramsey B, Mall MA, Taylor-Cousar JL, McKone EF, Tullis E, Floreth T, Michelson P, Sosnay PR, Nair N, Zahigian R, Martin H, Ahluwalia N, Lam A, Horsley A; VX20-121-102 Study Group; VX20-121-103 Study Group. Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. Lancet Respir Med. 2025 Mar;13(3):256-271. doi: 10.1016/S2213-2600(24)00411-9. Epub 2025 Jan 2.
PMID: 39756424DERIVEDHeneghan 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.
PMID: 37983082DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 29, 2021
First Posted
October 13, 2021
Study Start
October 27, 2021
Primary Completion
May 18, 2023
Study Completion
November 30, 2023
Last Updated
June 13, 2024
Results First Posted
June 13, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will not share
Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing