A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
- Registration Number
- NCT03447249
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 385
- Heterozygous for F508del and an MF mutation (as defined in the protocol)
- 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 Placebo Placebo Participants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period. VX-659/TEZ/IVA TC VX-659/TEZ/IVA Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period. VX-659/TEZ/IVA TC IVA Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
- Primary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline at Week 4 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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline through Week 24 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Number of Pulmonary Exacerbations (PEx) From Baseline through Week 24 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in Sweat Chloride (SwCl) From Baseline through Week 24 Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score From Baseline at Week 4 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 Body Mass Index (BMI) From Baseline at Week 24 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Absolute Change in Sweat Chloride From Baseline at Week 4 Sweat samples were collected using an approved collection device.
Time-to-first Pulmonary Exacerbation (PEx) From Baseline through Week 24 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline From Baseline at Week 24 BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
Absolute Change in Body Weight From Baseline at Week 24 Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks) Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA Pre-dose on Week 4, 8, 12, and 16
Trial Locations
- Locations (101)
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Stanford University
🇺🇸Palo Alto, California, United States
Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Lindenhofspital - Quartier Bleu
🇨🇭Bern, Switzerland
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
University of Tennessee Medical Center - Adult Cystic Fibrosis Clinic
🇺🇸Knoxville, Tennessee, United States
Sanford Research/ USD
🇺🇸Sioux Falls, South Dakota, United States
Providence Pediatric Pulmonary & Allergy/Immunology Clinic
🇺🇸Spokane, Washington, United States
Pneumologische Praxis Pasing
🇩🇪Muenchen, Germany
Hadassah Medical Organization
🇮🇱Jerusalem, Israel
St. Michael's Hospital
🇨🇦Toronto, Canada
Clinical Research of Charlotte
🇺🇸Charlotte, North Carolina, United States
Pediatric Pulmonary Unit Rambam Medical Center
🇮🇱Haifa, Israel
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Spain
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
Universitatsklinikum Schleswig-Holstein, Klinik fur Kinder- und Jugendmedizin
🇩🇪Lubeck, Germany
Royal Brisbane & Women's Hospital
🇦🇺Herston, Australia
John Hunter Hospital & Hunter Medical Research Institute
🇦🇺New Lambton Heights, Australia
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
🇩🇪Essen, Germany
Hospital Universitario Infantil La Paz
🇪🇸Madrid, Spain
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center
🇺🇸Philadelphia, Pennsylvania, United States
Coporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
University Hospital Cologne
🇩🇪Koeln, Germany
Prince Charles Hospital
🇦🇺Chermside, Australia
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
The Leeds Teaching Hospitals NHS Trust, St. James University Hospital
🇬🇧Leeds, United Kingdom
Queen Elizabeth II Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
Liverpool Heart and Chest Hospital
🇬🇧Liverpool, United Kingdom
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Charite Paediatric Pulmonology Department
🇩🇪Berlin, Germany
Clinic of J.W Goethe University
🇩🇪Frankfurt, Germany
Papworth Hospital NHS Foundation Trust, Papworth Everard
🇬🇧Cambridge, United Kingdom
Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
🇪🇸Barcelona, Spain
Princess Margaret Hospital for Children
🇦🇺Subiaco, Australia
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
University Hospital Llandough
🇬🇧Penarth, United Kingdom
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Miami/ Miller School of Medicine
🇺🇸Miami, Florida, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Indiana Clinical Research Center, IU Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Juliane Marie Center, Rigshospitalet
🇩🇰Copenhagen, Denmark
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Respiratory Diseases of Children and Adolescents
🇺🇸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 University Hospital Temple Street
🇮🇪Dublin, Ireland
Beaumont Hospital
🇮🇪Dublin, Ireland
Instytut Matki i Dziecka
🇵🇱Warsaw, Poland
University Hospital Limerick
🇮🇪Limerick, Ireland
Kinderspital Zuerich
🇨🇭Zürich, Switzerland
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Cork University Hospital
🇮🇪Dublin, Ireland
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
National University of Ireland
🇮🇪Galway, Ireland
Sheba Medical Center
🇮🇱Tel HaShomer, Israel
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
Universitaetsspital Zuerich
🇨🇭Zürich, Switzerland
Nottingham University Hospitals NHS Trust, Queens Medical Center
🇬🇧Nottingham, United Kingdom
Klinikum Innenstadt, University of Munich
🇩🇪München, Germany
Sydney Children's Hospital, Randwick
🇦🇺Randwick, Australia
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Hartford Health
🇺🇸Hartford, Connecticut, 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
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
The University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Kentucky Clinic
🇺🇸Lexington, Kentucky, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Helen DeVos Children's Hospital CF Center
🇺🇸Grand Rapids, Michigan, 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
Dartmouth Hitchcock Medical Center, Lebanon
🇺🇸Lebanon, New Hampshire, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Lung and Cystic Fibrosis Center at Women and Children's Hospital of Buffalo
🇺🇸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
Children's Foundation Research Center/ Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder - und Jugendmedizin
🇩🇪Jena, Germany
Schneider Children's Medical Center
🇮🇱Petah tikva, Israel
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
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 Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
🇬🇧Newcastle Upon Tyne, United Kingdom
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Kosair Charities Pediatric Clinical Research Unit
🇺🇸Louisville, Kentucky, United States
Yale New Haven Medical Center
🇺🇸New Haven, Connecticut, United States
Arnold Palmer Hospital
🇺🇸Orlando, Florida, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States