A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis (CF) Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)
2 other identifiers
interventional
435
12 countries
139
Brief Summary
The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous for F508del and a minimal function mutation (F/MF participants).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2021
139 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2021
CompletedFirst Posted
Study publicly available on registry
September 2, 2021
CompletedStudy Start
First participant enrolled
September 14, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 12, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 21, 2023
CompletedResults Posted
Study results publicly available
June 10, 2024
CompletedOctober 3, 2024
September 1, 2024
1.7 years
August 26, 2021
May 10, 2024
September 18, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (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 mmol/L (Pooled With Data From Study VX20-121-103)
From Baseline Through Week 24
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)
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:
- Heterozygous for F508del and a minimal function mutation (F/MF genotype)
- Forced expiratory volume in 1 second (FEV1) value \>=40% and \<=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 \>=40% and \<=80% for participants not currently receiving ELX/TEZ/IVA
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 (139)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner University of Arizona Medical Center
Tucson, Arizona, 85724, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Miller Children's Hospital / Long Beach Memorial
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Kaiser Permanente
Oakland, California, 94611, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
University of California San Francisco, Lung Transplant Program
San Francisco, California, 94143, United States
Children's Hospital of Colorado
Aurora, Colorado, 80045, United States
National Jewish Health
Denver, Colorado, 80206, United States
University of Florida, Shands Hospital
Gainesville, Florida, 32610, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center
Hollywood, Florida, 33021, United States
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803, United States
Nemours Children's Hospital
Orlando, Florida, 32827, 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
Augusta University
Augusta, Georgia, 30912, 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 Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, 40202, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, 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
Helen DeVos Children's Hospital CF Center
Grand Rapids, Michigan, 49503, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Childrens Hospital University of Missouri Health Sciences Center
Columbia, Missouri, 65212, United States
The Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Hospital - St. Louis University
St Louis, Missouri, 63104, United States
Washington University School of Medicine / St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
Billings Clinic
Billings, Montana, 59101, United States
Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Dartmouth Hitchcock, Manchester
Manchester, New Hampshire, 03104, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Albany Medical College
Albany, New York, 12208, 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
New York Medical College
Valhalla, New York, 10595, United States
Atrium Health Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27104, United States
Cleveland Clinic CF
Cleveland, Ohio, 44195, 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
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
Sanford Children's Speciality Clinic
Sioux Falls, South Dakota, 57105, United States
University of Tennessee Medical Center
Knoxville, Tennessee, 37920, United States
Children's Foundation Research Center / Le Bonheur Children's Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Driscoll Children's Hospital
Corpus Christi, Texas, 78411, 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
Texas Children's Hospital - Baylor College of Medicine
Houston, Texas, 77030, 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
Inova Fairfax
Falls Church, Virginia, 22042, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Royal Prince Alfred Hospital
Camperdown, Australia
The Prince Charles Hospital
Chermside, Australia
Alfred Hospital
Melbourne, VIC, Australia
Mater Adult Hospital
South Brisbane, Australia
Queensland Children's Hospital
South Brisbane, Australia
Westmead Hospital
Westmead, Australia
Klinika Detskych Infekcnich Nemoci
Brno, Czechia
Fakultni nemocnice v Motole
Prague, Czechia
Charite Paediatric Pulmonology Department
Berlin, Germany
St. Josef-Hospital
Bochum, 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
Johann Wolfgang Goethe University
Frankfurt, Germany
Hannover Medical School
Hanover, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Mukoviszidose-Zentrum am Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin
Jena, Germany
Johannes Gutenberg-Universitaet
Mainz, Germany
Klinikum Innenstadt, University of Munich
München, Germany
Pneumologisches Studienzentrum Muenchen-West
München, Germany
Klinikum Westbrandenburg (CF)
Potsdam, Germany
Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)
Ulm, Germany
Universitätsklinikum Würzburg
Würzburg, Germany
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 Health Ireland at Temple Street
Dublin, Ireland
St. Vincent's University Hospital
Dublin, Ireland
University Hospital Limerick (Adults)
Limerick, Ireland
University Hospital Limerick (Pediatrics)
Limerick, Ireland
Hadassah University Hospital Mount Scopus
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
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
Hospital de Santa Maria
Lisbon, Portugal
CHP - Hospital de Santo Antonio
Porto, Portugal
Hospital Sao Joao
Porto, Portugal
Hospital Saint Joan de Deu
Barcelona, Spain
Hospital Universitari Vall d Hebron
Barcelona, Spain
Hospital Infantil Universitario Nino Jesus
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Ramon y Cajal
Madrid, Spain
Hospital Virgen de la Arrixaca
Murcia, Spain
Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari
Sabadell, Spain
Hospital Universitario Virgen del Rocio
Seville, Spain
Hospital Universitario y Politecnico La Fe
Valencia, Spain
Sahlgrenska Universitetssjukhuset
Gothenburg, Sweden
Lund University Skanes Universitetssjukhus
Malmo, Sweden
Karolinska Universitetssjukhuset, Huddinge
Stockholm, Sweden
Birmingham Heartlands Hospital
Birmingham, United Kingdom
University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital
Bristol, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
Cambridge, United Kingdom
Royal Hospital for Sick Children
Edinburgh, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Clinical Research Facility, Queen Elizabeth University Hospital
Glasgow, United Kingdom
St. James University Hospital
Leeds, United Kingdom
Liverpool Heart and Chest Hospital
Liverpool, United Kingdom
King's College Hospital
London, United Kingdom
Royal Brompton Hospital
London, United Kingdom
St. Bartholomew's Hospital
London, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
Clinical Research Facility
Newcastle upon Tyne, 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
August 26, 2021
First Posted
September 2, 2021
Study Start
September 14, 2021
Primary Completion
May 12, 2023
Study Completion
November 21, 2023
Last Updated
October 3, 2024
Results First Posted
June 10, 2024
Record last verified: 2024-09
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