A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT03912233
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
- Part 1: Heterozygous for F508del and an MF mutation (F/MF)
- Part 2: Homozygous for F508del (F/F)
- FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height
Key
- History of clinically significant cirrhosis with or without portal hypertension
- 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
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: VX-121/TEZ/VX-561 TC - High Dose VX-121 Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. Part 1: Placebo Placebo Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period. Part 1: VX-121/TEZ/VX-561 TC - Low Dose VX-121 Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period Part 1: VX-121/TEZ/VX-561 TC - Low Dose TEZ Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period Part 1: VX-121/TEZ/VX-561 TC - Low Dose VX-561 Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period Part 1: VX-121/TEZ/VX-561 TC - Medium Dose TEZ Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Part 1: VX-121/TEZ/VX-561 TC - Medium Dose VX-561 Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Part 1: VX-121/TEZ/VX-561 TC - High Dose TEZ Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Part 1: VX-121/TEZ/VX-561 TC - High Dose VX-561 Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Part 2: TEZ/IVA TEZ/IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period. Part 2: TEZ/IVA IVA Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period. Part 2: VX-121/TEZ/VX-561 TC - High Dose TEZ Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. Part 2: VX-121/TEZ/VX-561 TC - High Dose VX-561 Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. Part 1: VX-121/TEZ/VX-561 TC - High Dose VX-121 Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Part 1: VX-121/TEZ/VX-561 TC - Medium Dose VX-121 Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
- 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 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2) 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 (SwCl) Concentrations From Baseline Through Day 29 Sweat samples were collected using an approved collection device.
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 Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) Pre-dose at Day 15 and Day 29
Trial Locations
- Locations (26)
HagaZiekenhuis van den Haag
🇳🇱Den Haag, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Pneumologisches Studienzentrum Muenchen-West
🇩🇪Muenchen, Germany
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
🇩🇪Essen, Germany
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
🇳🇱Heidelberglaan, Netherlands
Charite Paediatric Pulmonology Department
🇩🇪Berlin, Germany
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
🇬🇧Penarth, United Kingdom
University of Kentucky.
🇺🇸Lexington, Kentucky, United States
Keck Medical Center of University of Southern California
🇺🇸Los Angeles, California, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Santiago Reyes, M.D.
🇺🇸Oklahoma City, Oklahoma, United States
Academic Medical Center
🇳🇱Amsterdam, Netherlands
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Hospital de Santa Maria
🇵🇹Lisbon, Portugal
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
🇬🇧Newcastle Upon Tyne, United Kingdom
Kaiser Permanente
🇺🇸Oakland, California, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States