A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
2 other identifiers
interventional
271
13 countries
93
Brief Summary
This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).
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 Aug 2019
Shorter than P25 for phase_3
93 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
August 14, 2019
CompletedFirst Posted
Study publicly available on registry
August 15, 2019
CompletedStudy Start
First participant enrolled
August 28, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 12, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 12, 2020
CompletedResults Posted
Study results publicly available
July 2, 2021
CompletedJuly 2, 2021
June 1, 2021
10 months
August 14, 2019
June 11, 2021
June 11, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Week 8
Secondary Outcomes (6)
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group
From Baseline Through Week 8
Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group
From Baseline Through Week 8
Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group
From Baseline Through Week 8
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group
From Baseline Through Week 8
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group
From Baseline Through Week 8
- +1 more secondary outcomes
Study Arms (2)
Control: IVA or TEZ/IVA
ACTIVE COMPARATORFollowing an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
TC: ELX/TEZ/IVA
EXPERIMENTALFollowing an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
Interventions
FDC tablet for oral administration.
Mono-tablet for oral administration.
Fixed-dose combination (FDC) tablet for oral administration.
Eligibility Criteria
You may qualify if:
- Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
You may not qualify if:
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (93)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner University of Arizona Medical Center
Tucson, Arizona, 85724, United States
Miller Children's Hospital / Long Beach Memorial
Long Beach, California, 90806, United States
Stanford University
Palo Alto, California, 94304, 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
National Jewish Health
Denver, Colorado, 80206, United States
University of Miami Miller School of Medicine
Miami, Florida, 33136, United States
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803, United States
Indiana University
Indianapolis, Indiana, 46202, United States
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, 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
Michigan Medicine
Ann Arbor, Michigan, 48109-5212, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine / St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Northwell Health- Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
Mount Sinai Beth Israel
New York, New York, 10003, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27514, United States
UC Health Holmes
Cincinnati, Ohio, 45220, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, 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
Oregon Health & Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Dell Children's Medical Group
Austin, Texas, 78723, United States
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
University of Utah / Primary Children's Medical Center
Salt Lake City, Utah, 84132, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
The Prince Charles Hospital
Chermside, Australia
Alfred Hospital
Melbourne, VIC, Australia
Perth Children's Hospital
Nedlands, Australia
The Royal Children's Hospital
Parkville, VIC, Australia
Mater Adult Hospital
South Brisbane, Australia
Queensland Children's Hospital
South Brisbane, Australia
Westmead Hospital
Westmead, Australia
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
Stollery Children's Hospital
Edmonton, Canada
McGill University Health Center
Québec, Canada
St. Michael's Hospital
Toronto, Canada
St. Paul's Hospital
Vancouver, Canada
Juliane Marie Center, Rigshospitalet
Copenhagen, Denmark
Centre Hospitalier Lyon Sud
Benite Cedex, France
Groupe Hospitaler Pellegrin, CHU De Bordeaux
Bordeaux, France
CHRU de Lille - Hopital Albert Calmette
Lille, France
CHU Marseille - Hopital Nord
Marseille, France
CHU de Montpellier - Hopital Arnaud de Villeneuve
Montpellier, France
Hopital Cochin
Paris, France
Hopital Necker, Enfants Malades
Paris, France
Hopital Pontchaillou CHU de Rennes
Rennes, 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
Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin
Giessen, Germany
Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
Halle, Germany
Pneumologisches Studienzentrum Muenchen-West
München, Germany
University Hospital Wuerzburg
Würzburg, Germany
Cork University Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland
St. Vincent's University Hospital
Dublin, Ireland
University Hospital Limerick (Adults)
Limerick, Israel
Azienda Ospedaliero Universitaria Ospedale Riuniti
Ancona, Italy
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
Genova, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy
Malattie Apparato Respiratorio 2 - Fibrosi Cistica
Orbassano, Italy
Ospedale Pediatrico Bambino Gesu
Rome, Italy
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
Verona, Italy
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
HagaZiekenhuis van den Haag
The Hague, Netherlands
Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
Barcelona, Spain
Hospital Virgen de la Arrixaca
Murcia, Spain
Hospital Universitario Virgen del Rocio
Seville, Spain
Hospital Universitario y Politecnico La Fe
Valencia, Spain
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, 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
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Related Publications (1)
Barry PJ, Mall MA, Alvarez A, Colombo C, de Winter-de Groot KM, Fajac I, McBennett KA, McKone EF, Ramsey BW, Sutharsan S, Taylor-Cousar JL, Tullis E, Ahluwalia N, Jun LS, Moskowitz SM, Prieto-Centurion V, Tian S, Waltz D, Xuan F, Zhang Y, Rowe SM, Polineni D; VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825. doi: 10.1056/NEJMoa2100665.
PMID: 34437784DERIVED
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
- Restriction Type
- OTHER
- 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
- Expanded Access
- Yes
Study Record Dates
First Submitted
August 14, 2019
First Posted
August 15, 2019
Study Start
August 28, 2019
Primary Completion
June 12, 2020
Study Completion
June 12, 2020
Last Updated
July 2, 2021
Results First Posted
July 2, 2021
Record last verified: 2021-06
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