A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: TEZ/IVADrug: IVA
- Registration Number
- NCT03537651
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
- Eligible CFTR Mutation
- Pregnant and nursing females
- History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator
- Ongoing participation in another study with investigational drug
Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TEZ/IVA IVA Part A: Participants weighing less than (\<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (\>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing \<30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing \>=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age. TEZ/IVA TEZ/IVA Part A: Participants weighing less than (\<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (\>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing \<30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing \>=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age.
- Primary Outcome Measures
Name Time Method Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Day 1 up to Week 100
- Secondary Outcome Measures
Name Time Method Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group) From Parent Study 115 Baseline at Week 96 (Study 116) The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group) From Parent Study 115 Baseline at Week 96 (Study 116) BMI was defined as weight in kilograms (kg) divided by squared height in meters (m\^2).
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS From Parent Study 113B Baseline at Week 96 (Study 116) The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Part A: Absolute Change in BMI for 113B/116 FAS From Parent Study 113B Baseline at Week 96 (Study 116) BMI was defined as weight in kg divided by m\^2.
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group) From Parent Study 115 Baseline at Week 96 (Study 116) The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS From Parent Study 113B Baseline at Week 96 (Study 116) The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group) From Parent Study 115 Baseline at Week 96 (Study 116) Sweat samples were collected using an approved collection device.
Part A: Absolute Change in SwCl for 113B/116 FAS From Parent Study 113B Baseline at Week 96 (Study 116) Sweat samples were collected using an approved collection device.
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 up to Week 192
Trial Locations
- Locations (55)
St. Luke's CF Center of Idaho
🇺🇸Boise, Idaho, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Riley Hospital for Children Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital & Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Our Lady's Children's Hospital
🇮🇪Dublin, Ireland
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Kinderspital Zuerich
🇨ðŸ‡Zürich, Switzerland
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
🇬🇧London, United Kingdom
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Sanford Children's Speciality Clinic
🇺🇸Sioux Falls, South Dakota, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Johns Hopkins All Children's Hospital Outpatient Care Center
🇺🇸Saint Petersburg, Florida, United States
Dartmouth Hitchcock Medical Center
🇺🇸Manchester, New Hampshire, United States
UBMD Pediatrics/ CF Center of Western New York
🇺🇸Buffalo, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Austin Children's Chest Associates
🇺🇸Austin, Texas, United States
Universitair Ziekenhuis Brussel - Campus Jette
🇧🇪Brussels, Belgium
Perth Children's Hospital
🇦🇺Nedlands, Australia
Lady Cilento Children's Hospital
🇦🇺South Brisbane, Australia
McGill University Health Centre, Glen Site, Montreal Children's Hospital
🇨🇦Montreal, Quebec, Canada
Juliane Marie Center, Rigshopitalet
🇩🇰Copenhagen, Denmark
Hopital Necker, Enfants Malades
🇫🇷Paris Cedex 15, France
Clinic of J.W. Goethe University
🇩🇪Frankfurt, Germany
Groupe Hospitaler Pellegrin, CHU De Bordeaux
🇫🇷Bordeaux cedex, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
University Hospital Limerick
🇮🇪Limerick, Ireland
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Nemours/ Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Center for Advanced Pediatrics
🇺🇸Atlanta, Georgia, United States
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Inselspital - Universitaetsspital Bern
🇨ðŸ‡Bern, Switzerland
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
The Children's Hospital at Westmead
🇦🇺Westmead, Australia
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
🇦🇺New Lambton, Australia
British Columbia's Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Universitaetsklinikum Jena, Mukoviszidose-Zentrum
🇩🇪Jena, Germany
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
🇩🇪Giessen, Germany
Universitaetsklinkum Koeln, CF-Studienzentrum
🇩🇪Koeln, Germany
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
🇩🇪Tuebingen, Germany
Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
🇵🇱Lomianki, Poland