A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: TEZ/IVADrug: VX-445/TEZ/IVADrug: IVADrug: Placebo
- Registration Number
- NCT03525548
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This study will evaluate the efficacy of VX-445 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
- 113
- 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 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 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-445/TEZ/IVA TC Placebo Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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 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. VX-445/TEZ/IVA TC VX-445/TEZ/IVA Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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-445/TEZ/IVA TC IVA Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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.
- 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 Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA Day 1 and Week 4 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 Week 8) Absolute Change in Sweat Chloride (SwCl) From Baseline at Week 4 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 indicate fewer symptoms and better health-related quality of life.
Trial Locations
- Locations (44)
Universitair Ziekenhuis Brussel - Campus Jette
🇧🇪Brussels, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
HagaZiekenhuis van den Haag
🇳🇱Den Haag, Netherlands
University of Virginia Primary Care Center
🇺🇸Charlottesville, Virginia, United States
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Academic Medical Center
🇳🇱Amsterdam, Netherlands
The Royal Belfast Hospital for Sick Children
🇬🇧Belfast, United Kingdom
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Brussels, Belgium
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
🇳🇱Heidelberglaan, Netherlands
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
🇺🇸Toledo, Ohio, United States
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
🇺🇸Peoria, Illinois, United States
Miller Children's Hospital/ Long Beach Memorial
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Harper University Hospital
🇺🇸Detroit, Michigan, United States
UNC Marisco Clinical Research Center
🇺🇸Chapel Hill, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
🇺🇸Tampa, Florida, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Central Florida Pulmonary Group, PA
🇺🇸Orlando, Florida, United States
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
🇺🇸Boston, Massachusetts, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Vermont Lung Center
🇺🇸Colchester, Vermont, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States