A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: Placebo (matched to VX-659/TEZ/IVA)Drug: Placebo (matched to VX-659/TEZ/VX-561)Drug: TEZ/IVADrug: TEZDrug: IVA
- Registration Number
- NCT03224351
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
-
Body weight ≥35 kg.
-
Subjects must have an eligibleCFTR genotype.
- Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)
- Part 2: Homozygous for F508del (F/F)
-
FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
Key
- History of clinically significant cirrhosis with or without portal hypertension.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Lung infection with organisms associated with a more rapid decline in pulmonary status.
- History of 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 Part 3: VX-659/TEZ/VX-561 TC VX-659 Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks. Part 1: VX-659/TEZ/IVA TC - High Dose VX-659 Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 3: VX-659/TEZ/VX-561 TC VX-561 Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks. Part 1: VX-659/TEZ/IVA TC - Low Dose IVA Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - Low Dose VX-659 Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - High Dose TEZ/IVA Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - High Dose IVA Participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 2: TEZ/IVA IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Part 2: VX-659/TEZ/IVA TC TEZ/IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Part 1: Placebo Placebo (matched to VX-659/TEZ/IVA) Participants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - Low Dose TEZ/IVA Participants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - Medium Dose TEZ/IVA Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 1: VX-659/TEZ/IVA TC - Medium Dose IVA Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 2: TEZ/IVA TEZ/IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Part 3: Placebo Placebo (matched to VX-659/TEZ/VX-561) Participants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks. Part 1: VX-659/TEZ/IVA TC - Medium Dose VX-659 Participants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days. Part 2: VX-659/TEZ/IVA TC IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks. Part 3: VX-659/TEZ/VX-561 TC TEZ Participants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks. Part 2: VX-659/TEZ/IVA TC VX-659 Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
- Primary Outcome Measures
Name Time Method Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3) Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline Through Day 29 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 Sweat Chloride Concentrations From Baseline Through Day 29 Sweat samples were collected using an approved collection device.
Relative Change in ppFEV1 From Baseline Through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline at Day 29 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.
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561 Pre-dose at Day 15 and Day 29
Trial Locations
- Locations (46)
Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
🇺🇸New Brunswick, New Jersey, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
🇺🇸Baltimore, Maryland, United States
Sanford Research / USD
🇺🇸Sioux Falls, South Dakota, United States
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
🇺🇸Knoxville, Tennessee, United States
St. Vincent's University Hosptial
🇮🇪Dublin, Ireland
Schneider Children's Medical Center
🇮🇱Tikvah, Israel
Hadassah Medical Organization
🇮🇱Jerusalem, Israel
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
🇺🇸Morton Grove, Illinois, United States
The University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Helen DeVos Children's Hospital CF Center
🇺🇸Grand Rapids, Michigan, United States
Northwell Health, Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Albany Medical College
🇺🇸Albany, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Children's Foundation Research Center / Le Bonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Galway University Hospitals
🇮🇪Galway, Ireland
Providence Pediatric Pulmonary & Allergy/Immunology Clinic
🇺🇸Spokane, Washington, United States
Cork University Hospital
🇮🇪Cork, Ireland
University Hospital Limerick
🇮🇪Limerick, Ireland
Carmel Medical Center
🇮🇱Haifa, Israel
Ruth Children's Hospital Rambam Health Care Campus
🇬🇧Nottingham, United Kingdom
The Chaim Sheba medical center
🇮🇱Ramat Gan, Israel
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Papworth Hospital NHS Foundation Trust, Papworth Everard
🇬🇧Cambridge, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
🇬🇧Devon, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
🇬🇧Fulham, United Kingdom
Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
🇬🇧Glasgow, United Kingdom
Regional Respiratory Centre Belfast City Hospital
🇬🇧London, United Kingdom
Southampton University Hospitals NHS Foundation Trust
🇬🇧Hampshire, United Kingdom
Liverpool Heart and Chest Hospital
🇬🇧Merseyside, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Royal Brompton & Harefied NHS Foundation Trust
🇬🇧London, United Kingdom
University Hospital of South Manchester NHS Trust, North West Lung Centre
🇬🇧Manchester, United Kingdom
University of Miami/Miller School of Medicine
🇺🇸Miami, Florida, United States
Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Respiratory Diseases of Children & Adolescents
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah / Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University Hospital Llandough in Cardiff
🇬🇧Cardiff, United Kingdom
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States