A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: PlaceboDrug: VX-445/TEZ/IVADrug: IVA
- Registration Number
- NCT03525444
- 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 heterozygous for F508del and a minimal function mutation (F/MF subjects).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 405
- Heterozygous for the F508del mutation (F/MF)
- 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 Placebo Placebo Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period. VX-445/TEZ/IVA TC IVA Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period. VX-445/TEZ/IVA TC VX-445/TEZ/IVA Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 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 Absolute Change in Sweat Chloride (SwCl) From Baseline through Week 24 Sweat samples were collected using an approved collection device.
Number of Pulmonary Exacerbations (PEx) From Baseline through Week 24 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 Pulmonary Exacerbation (PEx) From Baseline through Week 24 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.
Absolute Change in Body Weight From Baseline at Week 24 Absolute Change in Sweat Chloride 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 indicating fewer symptoms and better health-related quality of life.
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline From Baseline at Week 24 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.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline through Week 24 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Body Mass Index (BMI) From Baseline at Week 24 BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
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 28 weeks) Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA Pre-dose on Week 4, 8, 12, and 16
Trial Locations
- Locations (115)
Maine Medical Partners
🇺🇸Portland, Maine, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Miller Children's Hospital/ Long Beach Memorial
🇺🇸Long Beach, California, United States
Kaiser Permanente
🇺🇸Oakland, California, United States
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Women & Children's Hospital
🇦🇺North Adelaide, Australia
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
🇺🇸Toledo, Ohio, United States
University of Wisconsin Hospitals and Clinics
🇺🇸Madison, Wisconsin, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Mater Adult Hospital
🇦🇺South Brisbane, Australia
Vermont Lung Center
🇺🇸Colchester, Vermont, United States
Saint Francis Medical Center/ Children's Hospital of Illinois/OSF
🇺🇸Peoria, Illinois, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
CHU de Nice - Hopital Pasteur
🇫🇷Nice, France
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
University of Calgary Medical Clinic of the Foothills Medical Centre
🇨🇦Calgary, Canada
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Azienda Ospedaliero Universitaria Ospedale Riuniti
🇮🇹Ancona, Italy
Dr. von Haunersches Kinderspital
🇩🇪München, Germany
The Royal Belfast Hospital for Sick Children
🇬🇧Belfast, United Kingdom
Heidelberg Cystic Fibrosis Center
🇩🇪Heidelberg, Germany
UMC St. Radboud
🇳🇱Nijmegen, Netherlands
Karolinska Univeritetssjukhuset, Huddinge
🇸🇪Stockholm, Sweden
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Massachusetts General Hospital Cystic Fibrosis Center
🇺🇸Boston, Massachusetts, United States
University Hospitals Cleveland Medical Center/ Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Valley Children's Hospital/ Children's Hospital of Central California
🇺🇸Madera, California, United States
Children's Speciality Services at North Druid Hills
🇺🇸Atlanta, Georgia, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Ann & Robert Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Specialty Care
🇺🇸Jacksonville, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of New Mexico Clinical & Translational Science Center
🇺🇸Albuquerque, New Mexico, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
The University of Texas Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
The Royal Children's Hospital
🇦🇺Parkville, Australia
Westmead Hospital
🇦🇺Westmead, Australia
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
University of Graz
🇦🇹Graz, Austria
Medizinische Universitat Innsbruck
🇦🇹Innsbruck, Austria
Medizinische Universitat Wien
🇦🇹Vienna, Austria
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Brussel - Campus Jette
🇧🇪Brussels, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
British Columbia's Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
McGill University Health Centre, Glen Site, Montreal Children's Hospital
🇨🇦Montréal, Quebec, Canada
Centre Hospitalier De L'Universite Laval
🇨🇦Qubec, Canada
Saint John Regional Hospital
🇨🇦Saint John, Canada
The Hospital for Sick Children
🇨🇦Toronto, Canada
Vancouver Island Health Authority
🇨🇦Victoria, Canada
Fakultni Nemocnice Brno
🇨🇿Brno, Czechia
Centre Hospitalier Lyon Sud
🇫🇷Benite Cedex, France
Groupe Hospitaler Pellegrin, CHU De Bordeaux
🇫🇷Bordeaux Cedex, France
CHU Marseille - Hopital Nord
🇫🇷Marseille, France
Hopital Cochin
🇫🇷Paris, France
Hopital Foch (Suresnes), Hopital Foch, Adultes
🇫🇷Suresnes, France
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
🇩🇪Erlangen, Germany
CHU de Rouen - Hopital Charles Nicolle
🇫🇷Rouen Cedex, Seine Maritime, France
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
🇩🇪Giessen, Germany
Hannover Medical School
🇩🇪Hannover, Germany
Johannes Gutenberg-Universitaet
🇩🇪Mainz, Germany
University Hospital Wuerzburg
🇩🇪Wuerzburg, Germany
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
🇩🇪Tuebingen, Germany
General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
🇬🇷Maroúsi, Greece
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
🇮🇹Firenze, Italy
HagaZiekenhuis van den Haag
🇳🇱Den Haag, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
🇬🇧Brimingham, United Kingdom
Royal Hospital for Sick Children
🇬🇧Edinburgh, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
UCSF Gateway Medical Center
🇺🇸San Francisco, California, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Harper University Hospital
🇺🇸Detroit, Michigan, United States
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
🇮🇹Genova, Italy
Azienda Ospedaliera Universitaria Policlinico G. Martino
🇮🇹Messina, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
🇮🇹Potenza, Italy
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
🇮🇹Verona, Italy
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
The Children's Hospital at Westmead
🇦🇺Westmead, Australia
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
UC Health Holmes
🇺🇸Cincinnati, Ohio, United States
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Central Florida Pulmonary Group
🇺🇸Orlando, Florida, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
🇺🇸Tampa, Florida, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
UNC Marsico Clinical Research Center
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
Universitaire Ziekenhuizen Leuven - Campus Gathuisberg
🇧🇪Leuven, Belgium
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
🇳🇱Heidelberglaan, Netherlands
University of Florida, Shands Hospital
🇺🇸Gainesville, Florida, United States
Tulane Medical Center
🇺🇸New Orleans, Louisiana, United States
Austin Children's Chest Associates
🇺🇸Austin, Texas, United States
Children's Hospital of Richmond at VCU, Children's Pavilion
🇺🇸Richmond, Virginia, United States
University of Virginia Primary Care Center
🇺🇸Charlottesville, Virginia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States