A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03447249 |
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Recruitment Status :
Completed
First Posted : February 27, 2018
Results First Posted : March 13, 2020
Last Update Posted : March 13, 2020
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Sponsor:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
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Brief Summary:
This study will evaluate the efficacy of VX-659 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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis | Drug: VX-659/TEZ/IVA Drug: IVA Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 385 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF) |
| Actual Study Start Date : | March 7, 2018 |
| Actual Primary Completion Date : | February 5, 2019 |
| Actual Study Completion Date : | February 5, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Cystic fibrosis
MedlinePlus related topics:
Cystic Fibrosis
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Participants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period.
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Drug: Placebo
Participants received placebo matched VX-659/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening. |
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Experimental: VX-659/TEZ/IVA TC
Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 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.
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Drug: VX-659/TEZ/IVA
Participants received VX-659/TEZ/IVA orally once daily in the morning.
Other Names:
Drug: IVA Participants received IVA orally once daily in the evening.
Other Names:
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Primary Outcome Measures :
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: 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 :
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline through Week 24 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Number of Pulmonary Exacerbations (PEx) [ Time Frame: 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 Sweat Chloride (SwCl) [ Time Frame: From Baseline through Week 24 ]Sweat samples were collected using an approved collection device.
- Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline through Week 24 ]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 Body Mass Index (BMI) [ Time Frame: From Baseline at Week 24 ]BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
- Absolute Change in Sweat Chloride [ Time Frame: 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 [ Time Frame: 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.
- Time-to-first Pulmonary Exacerbation (PEx) [ Time Frame: 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 BMI Z-score for Participants <=20 Years of Age at Baseline [ Time Frame: 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 Body Weight [ Time Frame: From Baseline at Week 24 ]
- Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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-659, TEZ, M1-TEZ, and IVA [ Time Frame: Pre-dose on Week 4, 8, 12, and 16 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Heterozygous for F508del and an MF mutation (as defined in the protocol)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key Exclusion Criteria:
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03447249
Locations
Hide 101 study locations
| United States, Alabama | |
| University of Alabama at Birmingham | |
| Birmingham, Alabama, United States, 35233 | |
| United States, California | |
| Stanford University | |
| Palo Alto, California, United States, 94304 | |
| United States, Colorado | |
| Children's Hospital Colorado | |
| Aurora, Colorado, United States, 80045 | |
| United States, Connecticut | |
| Hartford Health | |
| Hartford, Connecticut, United States, 06106 | |
| Yale New Haven Medical Center | |
| New Haven, Connecticut, United States, 06511 | |
| United States, Florida | |
| University of Miami/ Miller School of Medicine | |
| Miami, Florida, United States, 33136 | |
| Nicklaus Children's Hospital | |
| Miami, Florida, United States, 33155 | |
| Arnold Palmer Hospital | |
| Orlando, Florida, United States, 32806 | |
| Johns Hopkins All Children's Hospital Outpatient Care Center | |
| Saint Petersburg, Florida, United States, 33701 | |
| United States, Idaho | |
| St. Luke's CF Center of Idaho | |
| Boise, Idaho, United States, 83712 | |
| United States, Illinois | |
| Cystic Fibrosis Center of Chicago | |
| Glenview, Illinois, United States, 60025 | |
| Advocate Children's Hospital - Park Ridge/ North Suburban Pulmonary and Critical Care Consultants | |
| Niles, Illinois, United States, 60714 | |
| United States, Indiana | |
| Indiana Clinical Research Center, IU Health University Hospital | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Iowa | |
| The University of Iowa Hospitals and Clinics | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Kentucky | |
| Kentucky Clinic | |
| Lexington, Kentucky, United States, 40536 | |
| Kosair Charities Pediatric Clinical Research Unit | |
| Louisville, Kentucky, United States, 40202 | |
| United States, Maryland | |
| The Johns Hopkins Hospital | |
| Baltimore, Maryland, United States, 21287 | |
| United States, Massachusetts | |
| Boston Children's Hospital | |
| Boston, Massachusetts, United States, 02115 | |
| University of Massachusetts Memorial Medical Center | |
| Worcester, Massachusetts, United States, 01655 | |
| United States, Michigan | |
| University of Michigan Health System | |
| Ann Arbor, Michigan, United States, 48109 | |
| Helen DeVos Children's Hospital CF Center | |
| Grand Rapids, Michigan, United States, 49503 | |
| United States, Minnesota | |
| University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| United States, Mississippi | |
| University of Mississippi Medical Center | |
| Jackson, Mississippi, United States, 39216 | |
| United States, Missouri | |
| Children's Mercy Hospital | |
| Kansas City, Missouri, United States, 64108 | |
| Washington University School of Medicine/ St. Louis Children's Hospital | |
| Saint Louis, Missouri, United States, 63110 | |
| United States, New Hampshire | |
| Dartmouth Hitchcock Medical Center, Lebanon | |
| Lebanon, New Hampshire, United States, 03756 | |
| United States, New Jersey | |
| Rutgers-Robert Wood Johnson Medical School | |
| New Brunswick, New Jersey, United States, 80901 | |
| United States, New York | |
| Albany Medical College | |
| Albany, New York, United States, 12208 | |
| Lung and Cystic Fibrosis Center at Women and Children's Hospital of Buffalo | |
| Buffalo, New York, United States, 14222 | |
| Northwell Health, Long Island Jewish Medical Center | |
| New Hyde Park, New York, United States, 11040 | |
| Columbia University Medical Center | |
| New York, New York, United States, 10032 | |
| SUNY Upstate Medical University | |
| Syracuse, New York, United States, 13210 | |
| United States, North Carolina | |
| Clinical Research of Charlotte | |
| Charlotte, North Carolina, United States, 28277 | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | |
| Cincinnati, Ohio, United States, 45229 | |
| United States, Oklahoma | |
| Respiratory Diseases of Children and Adolescents | |
| Oklahoma City, Oklahoma, United States, 73112 | |
| United States, Oregon | |
| Oregon Health & Science University | |
| Portland, Oregon, United States, 97239 | |
| United States, Pennsylvania | |
| Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center | |
| Philadelphia, Pennsylvania, United States, 19017 | |
| Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center | |
| Pittsburgh, Pennsylvania, United States, 15224 | |
| United States, South Dakota | |
| Sanford Research/ USD | |
| Sioux Falls, South Dakota, United States, 57105 | |
| United States, Tennessee | |
| University of Tennessee Medical Center - Adult Cystic Fibrosis Clinic | |
| Knoxville, Tennessee, United States, 37920 | |
| Children's Foundation Research Center/ Le Bonheur Children's Hospital | |
| Memphis, Tennessee, United States, 38103 | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37920 | |
| United States, Texas | |
| Cook Children's Medical Center | |
| Fort Worth, Texas, United States, 76104 | |
| Baylor College of Medicine | |
| Houston, Texas, United States, 77030 | |
| United States, Utah | |
| University of Utah / Primary Children's Medical Center | |
| Salt Lake City, Utah, United States, 84132 | |
| United States, Washington | |
| Seattle Children's Hospital | |
| Seattle, Washington, United States, 98105 | |
| Providence Pediatric Pulmonary & Allergy/Immunology Clinic | |
| Spokane, Washington, United States, 99204 | |
| Australia, Victoria | |
| The Alfred Hospital | |
| Melbourne, Victoria, Australia | |
| Australia | |
| Royal Adelaide Hospital | |
| Adelaide, Australia | |
| Prince Charles Hospital | |
| Chermside, Australia | |
| Royal Brisbane & Women's Hospital | |
| Herston, Australia | |
| Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital | |
| Nedlands, Australia | |
| John Hunter Hospital & Hunter Medical Research Institute | |
| New Lambton Heights, Australia | |
| Sydney Children's Hospital, Randwick | |
| Randwick, Australia | |
| Princess Margaret Hospital for Children | |
| Subiaco, Australia | |
| Canada, Alberta | |
| Stollery Children's Hospital | |
| Edmonton, Alberta, Canada | |
| Canada, Nova Scotia | |
| Queen Elizabeth II Health Sciences Center | |
| Halifax, Nova Scotia, Canada | |
| Canada | |
| St. Michael's Hospital | |
| Toronto, Canada | |
| Denmark | |
| Juliane Marie Center, Rigshospitalet | |
| Copenhagen, Denmark | |
| Germany | |
| Charite Paediatric Pulmonology Department | |
| Berlin, Germany | |
| Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen | |
| Essen, Germany | |
| Clinic of J.W Goethe University | |
| Frankfurt, Germany | |
| Medizinische Hochschule Hannover | |
| Hannover, Germany | |
| Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder - und Jugendmedizin | |
| Jena, Germany | |
| University Hospital Cologne | |
| Koeln, Germany | |
| Universitatsklinikum Schleswig-Holstein, Klinik fur Kinder- und Jugendmedizin | |
| Lubeck, Germany | |
| Pneumologische Praxis Pasing | |
| Muenchen, Germany | |
| Klinikum Innenstadt, University of Munich | |
| München, Germany | |
| Ireland | |
| Beaumont Hospital | |
| Dublin, Ireland | |
| Children's University Hospital Temple Street | |
| Dublin, Ireland | |
| Cork University Hospital | |
| Dublin, Ireland | |
| Our Lady's Children's Hospital | |
| Dublin, Ireland | |
| St. Vincent's University Hospital | |
| Dublin, Ireland | |
| National University of Ireland | |
| Galway, Ireland | |
| University Hospital Limerick | |
| Limerick, Ireland | |
| Israel | |
| Lady Davis Carmel Medical Center | |
| Haifa, Israel | |
| Pediatric Pulmonary Unit Rambam Medical Center | |
| Haifa, Israel | |
| Hadassah Medical Organization | |
| Jerusalem, Israel | |
| Schneider Children's Medical Center | |
| Petah tikva, Israel | |
| Sheba Medical Center | |
| Tel HaShomer, Israel | |
| Poland | |
| Instytut Matki i Dziecka | |
| Warsaw, Poland | |
| Spain | |
| Hospital Universitari Vall d Hebron | |
| Barcelona, Spain | |
| Hospital Universitari Vall d'Hebron Servicio de Broncoscopia | |
| Barcelona, Spain | |
| Hospital Universitario 12 de Octubre | |
| Madrid, Spain | |
| Hospital Universitario Infantil La Paz | |
| Madrid, Spain | |
| Coporacio Sanitaria Parc Tauli | |
| Sabadell, Spain | |
| Hospital Universitario Virgen del Rocio | |
| Sevilla, Spain | |
| Hospital Universitario y Politecnico La Fe | |
| Valencia, Spain | |
| Switzerland | |
| Lindenhofspital - Quartier Bleu | |
| Bern, Switzerland | |
| Kinderspital Zuerich | |
| Zürich, Switzerland | |
| Universitaetsspital Zuerich | |
| Zürich, Switzerland | |
| United Kingdom | |
| Papworth Hospital NHS Foundation Trust, Papworth Everard | |
| Cambridge, United Kingdom | |
| Queen Elizabeth University Hospital | |
| Glasgow, United Kingdom | |
| The Leeds Teaching Hospitals NHS Trust, St. James University Hospital | |
| Leeds, United Kingdom | |
| Liverpool Heart and Chest Hospital | |
| Liverpool, United Kingdom | |
| Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital | |
| London, United Kingdom | |
| Wythenshawe Hospital | |
| Manchester, United Kingdom | |
| The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary | |
| Newcastle Upon Tyne, United Kingdom | |
| Nottingham University Hospitals NHS Trust, Queens Medical Center | |
| Nottingham, United Kingdom | |
| University Hospital Llandough | |
| Penarth, United Kingdom | |
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Study Documents (Full-Text)
Documents provided by Vertex Pharmaceuticals Incorporated:
Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol [PDF] April 27, 2018
Statistical Analysis Plan [PDF] February 22, 2019
| Responsible Party: | Vertex Pharmaceuticals Incorporated |
| ClinicalTrials.gov Identifier: | NCT03447249 |
| Other Study ID Numbers: |
VX17-659-102 2017-004132-11 ( EudraCT Number ) |
| First Posted: | February 27, 2018 Key Record Dates |
| Results First Posted: | March 13, 2020 |
| Last Update Posted: | March 13, 2020 |
| Last Verified: | March 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Cystic Fibrosis Fibrosis VX-659 Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases |
Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |