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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000184-89 | EudraCT Number |
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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 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-445/TEZ/IVA TC | Experimental | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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-445/TEZ/IVA | Drug | Participants received VX-445/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 |
|---|---|---|---|---|---|---|
| Banner University of Arizona Medical Center | Tucson | Arizona | 85724 | United States | ||
| University of Arkansas for Medical Sciences |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31679946 | Derived | Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31. |
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This study was conducted in participants with cystic fibrosis (CF) aged 12 years or older.
A total of 113 participants were enrolled in the study, of which 6 participants were included in the run-in period but were not dosed in TC treatment period. Results are presented for 107 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 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. |
| FG001 | VX-445/TEZ/IVA TC |
| 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 | Jul 19, 2018 | Dec 10, 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 to VX-445/TEZ/IVA orally once daily in the morning. |
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| Placebo | Drug | Participants received placebo matched 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 indicate fewer symptoms and better health-related quality of life.
| From Baseline at Week 4 |
| 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 Week 8) |
| Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA | Day 1 and Week 4 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Miller Children's Hospital/ Long Beach Memorial | Long Beach | California | 90806 | United States |
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Valley Children's Hospital | Madera | California | 93636 | United States |
| National Jewish Health | Denver | Colorado | 80206 | United States |
| Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital | Hollywood | Florida | 33021 | United States |
| Central Florida Pulmonary Group, PA | Orlando | Florida | 32803 | United States |
| Nemours Children's Hospital | Orlando | Florida | 32827 | United States |
| Tampa General Hospital Cardiac and Lung Transplant Clinic | Tampa | Florida | 33606 | United States |
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF | Peoria | Illinois | 61637 | United States |
| Tulane Medical Center | New Orleans | Louisiana | 70112 | United States |
| Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center | Boston | Massachusetts | 02114 | United States |
| Harper University Hospital | Detroit | Michigan | 48201 | United States |
| New York Medical College | Valhalla | New York | 10595 | United States |
| UNC Marisco Clinical Research Center | Chapel Hill | North Carolina | 27517 | United States |
| Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Dayton Children's Hospital | Dayton | Ohio | 45404 | United States |
| ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center | Toledo | Ohio | 43606 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| The University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Vermont Lung Center | Colchester | Vermont | 05446 | United States |
| University of Virginia Primary Care Center | Charlottesville | Virginia | 22908 | United States |
| West Virginia University | Morgantown | West Virginia | 26506 | United States |
| Cliniques Universitaires de Bruxelles Hopital Erasme | Brussels | Belgium |
| Universitair Ziekenhuis Brussel - Campus Jette | Brussels | Belgium |
| UZ Antwerpen | Edegem | Belgium |
| Universitair Ziekenhuis Gent | Ghent | Belgium |
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | Belgium |
| Academic Medical Center | Amsterdam | Netherlands |
| University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis | Heidelberglaan | Netherlands |
| UMC St. Radboud | Nijmegen | Netherlands |
| Erasmus Medical Center | Rotterdam | Netherlands |
| HagaZiekenhuis van den Haag | The Hague | Netherlands |
| The Royal Belfast Hospital for Sick Children | Belfast | United Kingdom |
| Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital | Birmingham | United Kingdom |
| Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital | Exeter | United Kingdom |
| Leeds General Infirmary | Leeds | United Kingdom |
| King's College Hospital | London | United Kingdom |
| Southampton General Hospital | Southampton | United Kingdom |
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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-445/TEZ/IVA TC | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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 | ||||||||||
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| 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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| 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. | 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 indicate 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 by 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-445, 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 | microgram per milliliter (mcg/mL) | 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 | 52 | 1 | 52 | 25 | 52 |
| EG001 | VX-445/TEZ/IVA TC | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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 | 55 | 2 | 55 | 24 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Respiration abnormal | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | 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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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Fatigue | General 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 | Sep 25, 2018 | Dec 10, 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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