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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001735-31 | EudraCT Number |
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This study will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TEZ/IVA | Active Comparator | Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks. |
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| ELX/TEZ/IVA | Experimental | Following TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ELX/TEZ/IVA | Drug | FDC tablet for oral administration. |
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| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in CF 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. | From Baseline Through Week 24 |
| 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 Through Week 24 |
| Absolute Change in Sweat Chloride (SwCl) |
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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 |
|---|---|---|---|---|---|---|
| The Prince Charles Hospital | Chermside | Australia | ||||
| Institute for Respiratory Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37983082 | Derived | Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4. | |
| 34942085 | Derived |
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Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent research/clinical-trial-data-sharing.
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This study was conducted in cystic fibrosis (CF) participants aged 12 years or older.
A total of 176 participants were enrolled in the study. Out of those 176 participants, 1 participant was randomized but not dosed in the treatment period. Therefore, results are presented for only 175 participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | TEZ/IVA | Following TEZ (tezacaftor)/IVA (ivacaftor) run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks. |
| FG001 | ELX/TEZ/IVA |
| 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 | May 30, 2019 | Jun 24, 2021 |
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| TEZ/IVA | Drug | Fixed-dose combination (FDC) tablet for oral administration. |
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| IVA | Drug | Mono tablet for oral administration. |
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Sweat samples were collected using an approved collection device. |
| From Baseline Through Week 24 |
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 in the 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 28) |
| Nedlands |
| Australia |
| Perth Children's Hospital | Nedlands | Australia |
| John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital | New Lambton | Australia |
| The Royal Children's Hospital | Parkville, VIC | Australia |
| Queensland Children's Hospital | South Brisbane | Australia |
| Universitair Ziekenhuis Brussel - Campus Jette | Brussels | Belgium |
| UZ Antwerpen | Edegem | Belgium |
| Universitair Ziekenhuis Gent | Ghent | Belgium |
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | Belgium |
| Charite Paediatric Pulmonology Department | Berlin | Germany |
| Universitaetsklinkum Koeln, CF-Studienzentrum | Cologne | Germany |
| Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen | Essen | Germany |
| Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie | Essen | Germany |
| Johann Wolfgang Goethe University | Frankfurt | Germany |
| Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin | Jena | Germany |
| Klinikum Innenstadt, University of Munich | München | Germany |
| Pneumologisches Studienzentrum Muenchen-West | München | Germany |
| Belfast City Hospital | Belfast | United Kingdom |
| University Hospitals Birmingham NHS Foundation Trust | Birmingham | United Kingdom |
| University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital | Bristol | United Kingdom |
| Papworth Hospital NHS Foundation Trust, Papworth Everard | Cambridge | United Kingdom |
| Western General Hospital | Edinburgh | United Kingdom |
| Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital | Exeter | United Kingdom |
| Clinical Research Facility, Queen Elizabeth University Hospital | Glasgow | United Kingdom |
| St. James University Hospital | Leeds | United Kingdom |
| Leeds General Infirmary | Leeds, West Yorkshire | United Kingdom |
| Alder Hey Children's Alder Hey Children's NHS Foundation Trust | Liverpool | United Kingdom |
| Great Ormond Street Hospital for Sick Children | London | United Kingdom |
| London and St Bartholomew's Hospital | London | United Kingdom |
| The University Hospital of South Manchester | 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 |
| All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough | Penarth | United Kingdom |
| Southampton General Hospital | Southampton | United Kingdom |
| Sutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, Van Braeckel E, Wainwright CE, Watson D, Ahluwalia N, Bruinsma BG, Harris C, Lam AP, Lou Y, Moskowitz SM, Tian S, Yuan J, Waltz D, Mall MA; VX18-445-109 study group. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022 Mar;10(3):267-277. doi: 10.1016/S2213-2600(21)00454-9. Epub 2021 Dec 20. |
| 33331662 | Derived | Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. |
Following TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | TEZ/IVA | Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. |
| BG001 | ELX/TEZ/IVA | Following TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. |
| 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/Ethnicity, Customized | Count of Participants | Participants |
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| CF 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. | Mean | Standard Deviation | units on a scale |
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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 in CF 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. | Full analysis set (FAS) included all randomized participants who carried the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in treatment period. | Posted | Least Squares Mean | Standard Error | units on a scale | From Baseline Through Week 24 |
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| Secondary | 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. | FAS. | Posted | Least Squares Mean | Standard Error | percentage points | From Baseline Through Week 24 |
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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 Through Week 24 |
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| Secondary | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Safety set included all participants who received at least 1 dose of study drug in the treatment period. | Posted | Number | participants | From Day 1 in the 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 28) |
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From Day 1 in the 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 28)
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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 TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. | 0 | 88 | 14 | 88 | 72 | 88 |
| EG001 | ELX/TEZ/IVA | Following TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. | 0 | 87 | 5 | 87 | 59 | 87 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Extrasystoles | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Distal intestinal obstruction syndrome | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Type 3 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Obsessive-compulsive disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Psychotic disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Bacterial test positive | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | 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 | Aug 2, 2020 | Jun 24, 2021 | 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 |
|---|---|
| C000706587 | elexacaftor, ivacaftor, tezacaftor drug combination |
| C000654124 | tezacaftor, ivacaftor drug combination |
| C545203 | ivacaftor |
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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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| White |
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| White, Asian |
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