A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
- Registration Number
- NCT03525574
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 507
- Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.
- History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.
- Current participation in an investigational drug trial (other than a parent study)
Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ELX/TEZ/IVA IVA Treatment Period: Participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hrs (q12h) in the treatment period for 192 weeks. Extension Period: Participants from certain countries participated in extension period and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks. ELX/TEZ/IVA ELX/TEZ/IVA Treatment Period: Participants received ELX 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hrs (q12h) in the treatment period for 192 weeks. Extension Period: Participants from certain countries participated in extension period and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the extension period for 48 weeks.
- Primary Outcome Measures
Name Time Method Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From Day 1 up to Week 196
- Secondary Outcome Measures
Name Time Method Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set From Baseline at Week 192 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in BMI Z-score for 103/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set From Baseline at Week 192 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time to First PEx for 103/105 Efficacy Set From Baseline at Week 192 Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in BMI Z-score for 102/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set From Baseline at Week 192 Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set From Baseline at Week 192 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set From Baseline at Week 192 Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set From Baseline at Week 192 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time to First PEx for 102/105 Efficacy Set From Baseline at Week 192 Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set From Baseline at Week 192 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change in Body Weight for 102/105 Efficacy Set From Baseline at Week 192 This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set From Baseline at Week 192 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. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Absolute Change in Body Weight for 103/105 Efficacy Set From Baseline at Week 192 This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set From Baseline at Week 192 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. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.
Trial Locations
- Locations (110)
Valley Children's Hospital
🇺🇸Madera, California, United States
Ann & Robert Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
New York Medical College
🇺🇸Valhalla, New York, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Vermont Lung Center
🇺🇸Colchester, Vermont, United States
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
🇺🇸Boston, Massachusetts, United States
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Billings Clinic Hospital
🇺🇸Billings, Montana, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
🇺🇸Toledo, Ohio, United States
Kaiser Permanente
🇺🇸Oakland, California, United States
Nemours Children's Specialty Care
🇺🇸Jacksonville, Florida, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center
🇺🇸Hollywood, Florida, United States
Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Children's Specialty Services at North Druid Hills
🇺🇸Atlanta, Georgia, United States
UNM Clinical and Translational Science Center
🇺🇸Albuquerque, New Mexico, United States
Maine Medical Partners
🇺🇸Portland, Maine, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
The Cystic Fibrosis Center, Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
UC Health Holmes
🇺🇸Cincinnati, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Virginia Primary Care Center
🇺🇸Charlottesville, Virginia, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Hospitals and Clinics
🇺🇸Madison, Wisconsin, United States
Women & Children's Hospital
🇦🇺North Adelaide, Australia
Westmead Hospital
🇦🇺Westmead, Australia
The Royal Children's Hospital
🇦🇺Parkville, Australia
Mater Misericordiae Ltd
🇦🇺South Brisbane, Australia
University of Graz
🇦🇹Graz, Austria
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
University of Calgary Medical Clinic of the Foothills Medical Centre
🇨🇦Calgary, Canada
Medizinische Universitat Wien
🇦🇹Vienna, Austria
Universitair Ziekenhuis Brussel - Campus Jette
🇧🇪Brussels, Belgium
McGill University Health Centre, Glen Site, Montreal Children's Hospital
🇨🇦Montreal, Canada
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Brussels, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Centre Hospitalier De L'Universite Laval
🇨🇦Quebec City, Canada
The Hospital for Sick Children
🇨🇦Toronto, Canada
Centre Hospitalier Lyon Sud
🇫🇷Benite Cedex, France
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
British Columbia's Children's Hospital
🇨🇦Vancouver, Canada
Fakultni Nemocnice Brno
🇨🇿Brno, Czechia
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
🇩🇪Erlangen, Germany
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Groupe Hospitaler Pellegrin, CHU De Bordeaux
🇫🇷Bordeaux cedex, France
CHU Marseille - Hopital Nord
🇫🇷Marseille, France
CHU de Rouen - Hopital Charles Nicolle
🇫🇷Rouen, France
Hopital Foch (Suresnes), Hopital Foch, Adultes
🇫🇷Suresnes, France
CHU de Nice - Hopital Pasteur
🇫🇷Nice, France
Hannover Medical School
🇩🇪Hannover, Germany
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
🇩🇪Giessen, Germany
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
🇩🇪Tuebingen, Germany
University Hospital Wuerzburg
🇩🇪Wurzburg, Germany
Johannes Gutenberg-Universitaet
🇩🇪Mainz, Germany
Dr. von Haunersches Kinderspital
🇩🇪München, Germany
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹Messina, Italy
General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
🇬🇷Maroussi, Greece
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
🇮🇹Firenze, Italy
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
🇮🇹Genova, Italy
Azienda Ospedaliero Universitaria Ospendali Riuniti
🇮🇹Ancona, Italy
HagaZiekenhuis van den Haag
🇳🇱Den Haag, Netherlands
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
🇮🇹Potenza, Italy
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
🇮🇹Verona, Italy
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
🇳🇱Heidelberglaan, Netherlands
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Karolinska Universitetssjukhuset, Huddinge
🇸🇪Stockholm, Sweden
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
St. Paul's Hospital
🇨🇦Vancouver, Canada
The Children's Hospital at Westmead
🇦🇺Westmead, Australia
Miller Children's Hospital / Long Beach Memorial
🇺🇸Long Beach, California, United States
UCSF Gateway Medical Center
🇺🇸San Francisco, California, United States
Harper University Hospital
🇺🇸Detroit, Michigan, United States
Hopital Cochin
🇫🇷Paris, France
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Central Florida Pulmonary Group, PA
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
🇺🇸Tampa, Florida, United States
UNC Marsico Clinical Research Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Florida, Shands Hospital
🇺🇸Gainesville, Florida, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital of Richmond at VCU, Children's Pavilion
🇺🇸Richmond, Virginia, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria