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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004133-82 | EudraCT Number |
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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 homozygous for the F508del mutation (F/F).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TEZ/IVA | Active Comparator | Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. |
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| VX-659/TEZ/IVA TC | Experimental | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-659/TEZ/IVA | Drug | Participants received VX-659/TEZ/IVA orally once daily in the morning. |
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| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | From Baseline at Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. | From Baseline at Week 4 |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Yale New Haven Medical Center |
This study was conducted in participants with cystic fibrosis (CF) aged 12 years or older.
A total of 116 participants were enrolled in the study, of which 5 participants were included in the run-in period but were not dosed in TC treatment period. Results are presented for 111 participants dosed in the TC treatment period.
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| ID | Title | Description |
|---|---|---|
| FG000 | TEZ/IVA | Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 27, 2018 | Sep 26, 2019 |
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| TEZ/IVA | Drug | Participants received TEZ/IVA orally once daily in the morning. |
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| IVA | Drug | Participants received IVA orally once daily in the evening. |
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| Placebo | Drug | Participants received placebo matched TEZ/IVA orally once daily in the morning. |
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| Placebo | Drug | Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning. |
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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.
| From Baseline at Week 4 |
| Safety and Tolerability as Assessed 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 Week 8) |
| Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA | From Day 1 and Week 4 |
| New Haven |
| Connecticut |
| 06511 |
| United States |
| University of Miami/Miller School of Medicine | Miami | Florida | 33136 | United States |
| St. Luke's CF Center of Idaho | Boise | Idaho | 83712 | United States |
| Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants | Niles | Illinois | 60714 | United States |
| Indiana Clinical Research Center, IU Health University Hospital | Indianapolis | Indiana | 46202 | United States |
| The University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| The Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Helen DeVos Children's Hospital CF Center | Grand Rapids | Michigan | 49503 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Washington University School of Medicine / St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Rutgers-Robert Wood Johnson Medical School | New Brunswick | New Jersey | 08901 | United States |
| Albany Medical College | Albany | New York | 12208 | United States |
| Northwell Health, Long Island Jewish Medical Center | New Hyde Park | New York | 11040 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| SUNY Upstate Medical University | Syracuse | New York | 13210 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Respiratory Diseases of Children and Adolescents | Oklahoma City | Oklahoma | 73211 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15224 | United States |
| Sanford Research/ USD | Sioux Falls | South Dakota | 57105 | United States |
| University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic | Knoxville | Tennessee | 37920 | United States |
| Children's Foundation Research Center/ Le Bonheur Children's Hospital | Memphis | Tennessee | 38103 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Utah/ Primary Children's Medical Center | Salt Lake City | Utah | 84132 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| The Alfred Hospital | Melbourne | Victoria | Australia |
| Royal Adelaide Hospital | Adelaide | Australia |
| Prince Charles Hospital | Chermside | Australia |
| Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital | Nedlands | Australia |
| John Hunter Hospital & Hunter Medical Research Institute | New Lambton Heights | Australia |
| Charite Paediatric Pulmonology Department | Berlin | Germany |
| Pneumologische Praxis Pasing | München | Germany |
| Cork University Hospital | Dublin | Ireland |
| Our Lady's Children's Hospital | Dublin | Ireland |
| St. Vincent's University Hospital | Dublin | Ireland |
| Hospital Universitari Vall d Hebron | Barcelona | Spain |
| Hospital Universitari Vall d'Hebron Servicio de Broncoscopia | Barcelona | Spain |
| Hospital Universitario Virgen del Rocio | Seville | Spain |
| Papworth Hospital NHS Foundation Trust, Papworth Everard | Cambridge | 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 |
| University Hospital Llandough | Penarth | United Kingdom |
| VX-659/TEZ/IVA TC |
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | TEZ/IVA | Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
| BG001 | VX-659/TEZ/IVA TC | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Forced Expiratory Volume in 1 Second (ppFEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Mean | Standard Deviation | percentage points |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Full analysis set (FAS) included all randomized participants who carried the intended CF transmembrane conductance regulator gene (CFTR) allele mutation and received at least 1 dose of study drug in the TC Treatment Period. | Posted | Least Squares Mean | Standard Error | percentage points | From Baseline at Week 4 |
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| Secondary | Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. | FAS. | Posted | Least Squares Mean | Standard Error | millimole per liter (mmol/L) | From Baseline at Week 4 |
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| Secondary | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | 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. | FAS. | Posted | Least Squares Mean | Standard Error | units on a scale | From Baseline at Week 4 |
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| Secondary | Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Safety set included all participants who received at least 1 dose of study drug in the TC treatment period. | Posted | Number | participants | 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 Week 8) |
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| Secondary | Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA | Pharmacokinetic analysis set included all participants who received at least 1 dose of study drug in the TC treatment period. Here "Number analyzed" signifies those participants who were evaluable at specified time points. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | From Day 1 and Week 4 |
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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 Week 8)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TEZ/IVA | Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. | 0 | 57 | 0 | 57 | 19 | 57 |
| EG001 | VX-659/TEZ/IVA TC | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. | 0 | 54 | 2 | 54 | 23 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | 617-341-6777 | medicalinfo@vrtx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 7, 2018 | Sep 26, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| C545203 | ivacaftor |
| C000654124 | tezacaftor, ivacaftor drug combination |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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