A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT03460990
- 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 homozygous for the F508del mutation (F/F).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
- Homozygous for the F508del mutation (F/F)
- 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 VX-659/TEZ/IVA TC VX-659/TEZ/IVA Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. TEZ/IVA Placebo Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. VX-659/TEZ/IVA TC IVA Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. VX-659/TEZ/IVA TC Placebo Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. TEZ/IVA TEZ/IVA Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. TEZ/IVA IVA Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (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 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.
Safety and Tolerability as Assessed 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 Week 8) Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA From Day 1 and Week 4 Absolute Change in Sweat Chloride (SwCl) From Baseline at Week 4 Sweat samples were collected using an approved collection device.
Trial Locations
- Locations (46)
Yale New Haven Medical Center
🇺🇸New Haven, Connecticut, United States
St. Luke's CF Center of Idaho
🇺🇸Boise, Idaho, United States
Helen DeVos Children's Hospital CF Center
🇺🇸Grand Rapids, Michigan, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Sanford Research/ USD
🇺🇸Sioux Falls, South Dakota, 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
Charite Paediatric Pulmonology Department
🇩🇪Berlin, Germany
Cork University Hospital
🇮🇪Dublin, Ireland
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Miami/Miller School of Medicine
🇺🇸Miami, Florida, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
🇺🇸Niles, Illinois, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, 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
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Indiana Clinical Research Center, IU Health University Hospital
🇺🇸Indianapolis, Indiana, United States
The University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Prince Charles Hospital
🇦🇺Chermside, Australia
Pneumologische Praxis Pasing
🇩🇪Muenchen, Germany
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
John Hunter Hospital & Hunter Medical Research Institute
🇦🇺New Lambton Heights, Australia
Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
🇪🇸Barcelona, Spain
Hospital Universitari Vall d Hebron
🇪🇸Barcelona, Spain
Papworth Hospital NHS Foundation Trust, Papworth Everard
🇬🇧Cambridge, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
Liverpool Heart and Chest Hospital
🇬🇧Liverpool, United Kingdom
University Hospital Llandough
🇬🇧Penarth, United Kingdom
University of Utah/ Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Respiratory Diseases of Children and Adolescents
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Northwell Health, Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
St. Vincent's University Hospital
🇮🇪Dublin, Ireland