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)
- Registration Number
- NCT04058353
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 271
- 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
Key
- 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
Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control: IVA or TEZ/IVA IVA Following 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. Control: IVA or TEZ/IVA TEZ/IVA Following 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 ELX/TEZ/IVA Following 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. TC: ELX/TEZ/IVA IVA Following 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.
- Primary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group From Baseline Through Week 8 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Secondary Outcome Measures
Name Time Method Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group From Baseline Through Week 8 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group From Baseline Through Week 8 Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group From Baseline Through Week 8 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.
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group From Baseline Through Week 8 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.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Day 1 up to Week 12 Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group From Baseline Through Week 8 Sweat samples were collected using an approved collection device.
Trial Locations
- Locations (93)
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
🇺🇸Boston, Massachusetts, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Brussel - Campus Jette
🇧🇪Brussels, Belgium
HagaZiekenhuis van den Haag
🇳🇱Den Haag, Netherlands
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
University of North Carolina Hospitals
🇺🇸Chapel Hill, North Carolina, United States
University of Utah / Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco, Lung Transplant Program
🇺🇸San Francisco, California, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Beaumont Hospital
🇮🇪Dublin, Ireland
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
🇮🇹Verona, Italy
Papworth Hospital NHS Foundation Trust, Papworth Everard
🇬🇧Cambridge, United Kingdom
Centre Hospitalier Lyon Sud
🇫🇷Benite Cedex, France
Groupe Hospitaler Pellegrin, CHU De Bordeaux
🇫🇷Bordeaux cedex, France
CHU Marseille - Hopital Nord
🇫🇷Marseille, France
Mater Adult Hospital
🇦🇺South Brisbane, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Charite Paediatric Pulmonology Department
🇩🇪Berlin, Germany
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
CHRU de Lille - Hopital Albert Calmette
🇫🇷Lille, France
Clinical Research Facility, Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
St. Paul's Hospital
🇨🇦Vancouver, Canada
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
McGill University Health Center
🇨🇦Québec, Canada
Queensland Children's Hospital
🇦🇺South Brisbane, Australia
Hopital Pontchaillou CHU de Rennes
🇫🇷Rennes Cedex, France
Hopital Cochin
🇫🇷Paris, France
St. Michael's Hospital
🇨🇦Toronto, Canada
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
🇩🇪Essen, Germany
CHU de Montpellier - Hopital Arnaud de Villeneuve
🇫🇷Montpellier Cedex 5, France
Juliane Marie Center, Rigshospitalet
🇩🇰Copenhagen, Denmark
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Hopital Necker, Enfants Malades
🇫🇷Paris Cedex 15, France
Stollery Children's Hospital
🇨🇦Edmonton, Canada
Cork University Hospital
🇮🇪Cork, Ireland
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Azienda Ospedaliero Universitaria Ospedale Riuniti
🇮🇹Ancona, Italy
St. James University Hospital
🇬🇧Leeds, United Kingdom
Liverpool Heart and Chest Hospital
🇬🇧Liverpool, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
University Hospital Wuerzburg
🇩🇪Würzburg, Germany
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
🇩🇪Erlangen, Germany
Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
🇩🇪Halle, Germany
Pneumologisches Studienzentrum Muenchen-West
🇩🇪Muenchen, Germany
Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
🇪🇸Barcelona, Spain
Hospital Virgen de la Arrixaca
🇪🇸Murcia, Spain
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Central Florida Pulmonary Group, PA
🇺🇸Orlando, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
The University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Washington University School of Medicine / St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Northwell Health- Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
UC Health Holmes
🇺🇸Cincinnati, Ohio, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
🇺🇸Toledo, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Dell Children's Medical Group
🇺🇸Austin, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Alfred Hospital
🇦🇺Melbourne, VIC, Australia
The Prince Charles Hospital
🇦🇺Chermside, Australia
Perth Children's Hospital
🇦🇺Nedlands, Australia
The Royal Children's Hospital
🇦🇺Parkville, VIC, Australia
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin
🇩🇪Giessen, Germany
University Hospital Limerick (Adults)
🇮🇱Limerick, Israel
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
🇮🇹Genova, Italy
Malattie Apparato Respiratorio 2 - Fibrosi Cistica
🇮🇹Orbassano, Italy
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
🇳🇱Heidelberglaan, Netherlands
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
Stanford University
🇺🇸Palo Alto, California, United States
Miller Children's Hospital / Long Beach Memorial
🇺🇸Long Beach, California, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States