A Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy
- Registration Number
- NCT03447262
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This study will evaluate the long-term safety and tolerability of VX-659 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 484
- Completed study drug treatment in a parent study; 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description VX-659/TEZ/IVA TC IVA Participants from parent studies VX17-659-102 (NCT03447249) or VX17-659-103 (NCT03460990) were administered VX-659 240 milligrams (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the TC treatment period for up to 96 weeks in the current study VX17-659-105. VX-659/TEZ/IVA TC VX-659/TEZ/IVA Participants from parent studies VX17-659-102 (NCT03447249) or VX17-659-103 (NCT03460990) were administered VX-659 240 milligrams (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the TC treatment period for up to 96 weeks in the current study VX17-659-105.
- Primary Outcome Measures
Name Time Method Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)
- Secondary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102 From Baseline at Week 72 (Study 659-105) FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline) From Baseline at Week 60 (Study 659-105) BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in Body Weight for Participants From the Parent Study 659-103 From Baseline at Week 72 (Study 659-105) The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in ppFEV1 for Participants From the Parent Study 659-103 From Baseline at Week 72 (Study 659-105) FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in SwCl for Participants From the Parent Study 659-103 From Baseline at Week 24 (Study 659-105) Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Number of Participants With at Least One PEx for Participants From the Parent Study 659-102 From Baseline up to Week 96 (Study 659-105) PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Absolute Change in BMI for Participants From the Parent Study 659-103 From Baseline at Week 72 (Study 659-105) BMI was defined as weight in kg divided by squared height in meters (m\^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Number of Participants With at Least One PEx for Participants From the Parent Study 659-103 From Baseline up to Week 96 (Study 659-105) PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103 From Baseline at Week 72 (Study 659-105) 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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102 From Baseline up to Week 96 (Study 659-105) PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Absolute Change in Body Weight for Participants From the Parent Study 659-102 From Baseline at Week 72 (Study 659-105) The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102 From Baseline at Week 24 (Study 659-105) Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Number of PEx for Participants From the Parent Study 659-103 From Baseline up to Week 96 (Study 659-105) PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102 From Baseline at Week 72 (Study 659-105) BMI was defined as weight in kilograms (kg) divided by squared height in meters (m\^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102 From Baseline at Week 72 (Study 659-105) 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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline) From Baseline at Week 60 (Study 659-105) BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Trial Locations
- Locations (100)
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Drexel University College of Medicine / Drexel Adult Cystic Fibrosis Center
🇺🇸Philadelphia, Pennsylvania, United States
Cork University Hospital
🇮🇪Cork, Ireland
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Indiana Clinical Research Center, IU Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Lady Cilento Children's Hospital
🇦🇺South Brisbane, Australia
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Spain
Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
🇪🇸Barcelona, Spain
Kinderspital Zuerich
🇨🇭Zürich, Switzerland
Liverpool Head and Chest Hospital
🇬🇧Liverpool, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Santiago Reyes, M.D.
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah/ Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Alfred Hospital
🇦🇺Melbourne, Australia
Stanford University
🇺🇸Palo Alto, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Yale New Haven Medical Center
🇺🇸New Haven, Connecticut, United States
Orlando Health, Inc.- Arnold Palmer Hospital for Children (APH)
🇺🇸Orlando, Florida, United States
St. Luke's CF Center of Idaho
🇺🇸Boise, Idaho, United States
Johns Hopkins All Children's Hospital Outpatient Care Center
🇺🇸Saint Petersburg, Florida, United States
Cystic Fibrosis Center of Chicago
🇺🇸Glenview, Illinois, United States
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
🇺🇸Niles, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Kosair Charities Pediatric Clinical Research Unit
🇺🇸Louisville, Kentucky, United States
The University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
🇺🇸Grand Rapids, Michigan, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Dartmouth Hitchcock, Manchester
🇺🇸Manchester, New Hampshire, United States
Washington University School of Medicine/ St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Albany Medical College
🇺🇸Albany, New York, United States
CF Therapeutics Development Center of Western New York
🇺🇸Buffalo, New York, United States
Northwell Health, Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Clinical Research of Charlotte
🇺🇸Charlotte, North Carolina, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Sanford Children's Specialty Clinic
🇺🇸Sioux Falls, South Dakota, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Foundation Research Center / Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
University of Tennessee Medical Center- Adult Cystic Fibrosis Clinic
🇺🇸Knoxville, Tennessee, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
🇺🇸Spokane, Washington, United States
Institute for Respiratory Health, Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
The Prince Charles Hospital
🇦🇺Chermside, Australia
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
🇦🇺New Lambton, Australia
Telethon Kids Institute
🇦🇺Perth, Australia
Sydney Children's Hospital
🇦🇺Randwick, Australia
St. Michael's Hospital
🇨🇦Toronto, Canada
Stollery Children's Hospital
🇨🇦Edmonton, Canada
Queen Elizabeth II Health Sciences Center
🇨🇦Halifax, Canada
Charite Paediatric Pulmonology Department
🇩🇪Berlin, Germany
Juliane Marie Center, Rigshospitalet
🇩🇰Copenhagen, Denmark
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Clinic of J.W. Goethe University
🇩🇪Frankfurt, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
🇩🇪Essen, Germany
Universitaetsklinkum Koeln, CF-Studienzentrum
🇩🇪Koeln, Germany
Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
🇩🇪Jena, Germany
Klinikum Innenstadt, University of Munich
🇩🇪München, Germany
Beaumont Hospital
🇮🇪Dublin, Ireland
Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
🇩🇪Lubeck, Germany
Pneumologische Praxis Pasing
🇩🇪Muenchen, Germany
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
University Hospital Galway
🇮🇪Galway, Ireland
University Hospital Limerick
🇮🇪Limerick, Ireland
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Temple Street Children's University Hospital
🇮🇪Dublin, Ireland
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Rambam Health Care Campus, Liver Unit
🇮🇱Haifa, Israel
Pediatrics Hadassah Medical Center
🇮🇱Jerusalem, Israel
Schneider Children's Medical Center
🇮🇱Petah Tikva, Israel
Sheba Medical Center
🇮🇱Tel HaShomer, Israel
Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
🇵🇱Łomianki, Poland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Infantil La Paz
🇪🇸Madrid, Spain
Lindenhofspital - Quartier Bleu
🇨🇭Bern, Switzerland
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Parc Tauli Sabadell Hospital Universitari
🇪🇸Sabadell, Spain
Papworth Hospital NHS Foundation Trust, Papworth Everard
🇬🇧Cambridge, United Kingdom
St. James University Hospital
🇬🇧Leeds, United Kingdom
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Clinical Research Facility, Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
Wythenshaw e Hospital
🇬🇧Manchester, United Kingdom
Wolfson Cystic Fibrosis Unit, City Campus
🇬🇧Nottingham, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
🇬🇧Newcastle Upon Tyne, United Kingdom
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
🇬🇧Penarth, United Kingdom