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This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivacaftor (Run-in Period) | Experimental | Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. |
|
| VX-661 + Ivacaftor (Active comparator period) | Experimental | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. |
|
| Ivacaftor monotherapy (Active comparator period) | Active Comparator | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivacaftor | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Baseline, Through Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Baseline, Through Week 8 |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33339768 | Derived | McKone EF, DiMango EA, Sutharsan S, Barto TL, Campbell D, Ahluwalia N, Higgins M, Owen CA, Tullis E. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021 Mar;20(2):234-242. doi: 10.1016/j.jcf.2020.11.003. Epub 2020 Dec 16. |
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The study consisted of 2 periods: an Ivacaftor Run-in Period and an Active Comparator Treatment Period. Participants were randomized in a ratio of 1:1 to receive either VX-661/ivacaftor combination therapy or ivacaftor monotherapy for 8 weeks during the Active Comparator Treatment Period after completion of 4 weeks Ivacaftor Run-in Period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ivacaftor (Run-in Period) | Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. |
| FG001 | VX-661 + Ivacaftor (Active Comparator Period) | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Ivacaftor Run-in Period (4 Weeks) |
|
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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 18, 2017 | Sep 28, 2018 |
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| Tezacaftor/Ivacaftor | Drug |
|
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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. |
| Baseline, Through Week 8 |
| Absolute Change From Baseline in Sweat Chloride Through Week 8 | Sweat samples were collected using an approved collection device. | Baseline, Through Week 8 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Week 16 |
| Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA) | Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period |
| Oakland |
| California |
| United States |
| San Diego | California | United States |
| Aurora | Colorado | United States |
| Washington D.C. | District of Columbia | United States |
| Orlando | Florida | United States |
| Augusta | Georgia | United States |
| Indianapolis | Indiana | United States |
| Lexington | Kentucky | United States |
| Boston | Massachusetts | United States |
| Ann Arbor | Michigan | United States |
| Detroit | Michigan | United States |
| Grand Rapids | Michigan | United States |
| St Louis | Missouri | United States |
| Omaha | Nebraska | United States |
| Lebanon | New Hampshire | United States |
| Manchester | New Hampshire | United States |
| Morristown | New Jersey | United States |
| New Brunswick | New Jersey | United States |
| Albany | New York | United States |
| New York | New York | United States |
| Cincinnati | Ohio | United States |
| Toledo | Ohio | United States |
| Oklahoma City | Oklahoma | United States |
| Portland | Oregon | United States |
| Philadelphia | Pennsylvania | United States |
| Pittsburgh | Pennsylvania | United States |
| Charleston | South Carolina | United States |
| Knoxville | Tennessee | United States |
| Nashville | Tennessee | United States |
| Houston | Texas | United States |
| Salt Lake City | Utah | United States |
| Morgantown | West Virginia | United States |
| Chermside | Australia |
| Clayton | Australia |
| Melbourne | Australia |
| South Brisbane | Australia |
| Westmead | Australia |
| Innsbruck | Austria |
| Brussels | Belgium |
| Ghent | Belgium |
| Leuven | Belgium |
| Calgary | Canada |
| Toronto | Canada |
| Vancouver | Canada |
| Paris | France |
| Dresden | Germany |
| Erlangen | Germany |
| Essen | Germany |
| Frankfurt | Germany |
| Giessen | Germany |
| Heidelberg | Germany |
| Jena | Germany |
| München | Germany |
| Cork | Ireland |
| Dublin | Ireland |
| Bari | Italy |
| Milan | Italy |
| Roma | Italy |
| Belfast | United Kingdom |
| Birmingham | United Kingdom |
| Cardiff | United Kingdom |
| Glasgow | United Kingdom |
| Leeds | United Kingdom |
| London | United Kingdom |
| Manchester | United Kingdom |
| Newcastle | United Kingdom |
| Southampton | United Kingdom |
| FG002 | Ivacaftor Monotherapy (Active Comparator Period) | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| Active Comparator Period (8 Weeks) |
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Baseline analysis population included all participants who were included in Full Analysis Set for active comparator period (all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period.)
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| ID | Title | Description |
|---|---|---|
| BG000 | VX-661 + Ivacaftor (Active Comparator Period) | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. |
| BG001 | Ivacaftor Monotherapy (Active Comparator Period) | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome. | Posted | Least Squares Mean | Standard Error | Percent predicted of FEV1 | Baseline, Through Week 8 |
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| Secondary | Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome. | Posted | Least Squares Mean | Standard Error | Percent change | Baseline, Through Week 8 |
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| Secondary | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8 | 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. | Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Through Week 8 |
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| Secondary | Absolute Change From Baseline in Sweat Chloride Through Week 8 | Sweat samples were collected using an approved collection device. | Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome. | Posted | Least Squares Mean | Standard Error | Millimoles per liter | Baseline, Through Week 8 |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | The Safety Set included all participants who received at least 1 dose of study drug during Ivacaftor (Run-in period) and active comparator treatment period. | Posted | Number | Participants | Baseline up to Week 16 |
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| Secondary | Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA) | Pharmacokinetic (PK) set included participants who received study drug and had PK assessment. Here 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome. "Number Analyzed=0" indicates no participants were analyzed for specified categories because VX-661 was not administered in the specified arms. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period |
|
Baseline up to Week 16
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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 | Ivacaftor (Run-in Period) | Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. | 0 | 156 | 2 | 156 | 24 | 156 |
| EG001 | VX-661 + Ivacaftor (Active Comparator Period) | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. | 0 | 76 | 4 | 76 | 25 | 76 |
| EG002 | Ivacaftor Monotherapy (Active Comparator Period) | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. | 0 | 75 | 7 | 75 | 32 | 75 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Human rhinovirus test positive | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Idiopathic intracranial hypertension | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Infective exacerbation of bronchiectasis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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PI is free to publish results of the study after (1)first multi-center publication, (2)if sponsor elects not to publish the results, or(3)18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
| 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 | Jul 28, 2017 | Sep 28, 2018 | 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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| Lost to Follow-up |
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| Other non-compliance |
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| Other |
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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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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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