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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-002835-76 | 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 heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control: IVA or TEZ/IVA | Active Comparator | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks. |
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| TC: ELX/TEZ/IVA | Experimental | Following an IVA or 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 8 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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | From Baseline Through Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group | Sweat samples were collected using an approved collection device. | From Baseline Through Week 8 |
| Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group |
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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 | ||
| Banner University of Arizona Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34437784 | Derived | Barry PJ, Mall MA, Alvarez A, Colombo C, de Winter-de Groot KM, Fajac I, McBennett KA, McKone EF, Ramsey BW, Sutharsan S, Taylor-Cousar JL, Tullis E, Ahluwalia N, Jun LS, Moskowitz SM, Prieto-Centurion V, Tian S, Waltz D, Xuan F, Zhang Y, Rowe SM, Polineni D; VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825. doi: 10.1056/NEJMoa2100665. |
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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 271 participants were enrolled in this study out of which 12 participants discontinued in run-in period. Of 259 participants, 1 participant was randomized but not dosed in the treatment period. Therefore, results are presented for only 258 participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control: IVA or TEZ/IVA | Following an IVA (ivacaftor) or TEZ (tezacaftor)/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks. |
| FG001 | Triple Combination (TC): 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 | Dec 2, 2019 | May 7, 2021 |
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| IVA | Drug | Mono-tablet for oral administration. |
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| TEZ/IVA | Drug | Fixed-dose combination (FDC) tablet for oral administration. |
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
| From Baseline Through Week 8 |
| Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group | Sweat samples were collected using an approved collection device. | From Baseline Through Week 8 |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group | 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 8 |
| Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group | 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 8 |
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 12 |
| Tucson |
| Arizona |
| 85724 |
| United States |
| Miller Children's Hospital / Long Beach Memorial | Long Beach | California | 90806 | United States |
| Stanford University | Palo Alto | California | 94304 | United States |
| University of California Davis Medical Center | Sacramento | California | 95817 | United States |
| University of California San Francisco, Lung Transplant Program | San Francisco | California | 94143 | United States |
| National Jewish Health | Denver | Colorado | 80206 | United States |
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States |
| Central Florida Pulmonary Group, PA | Orlando | Florida | 32803 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| The University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
| Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center | Boston | Massachusetts | 02114 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Michigan Medicine | Ann Arbor | Michigan | 48109-5212 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Washington University School of Medicine / St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| Northwell Health- Long Island Jewish Medical Center | New Hyde Park | New York | 11040 | United States |
| Mount Sinai Beth Israel | New York | New York | 10003 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| University of North Carolina Hospitals | Chapel Hill | North Carolina | 27514 | United States |
| UC Health Holmes | Cincinnati | Ohio | 45220 | 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 |
| 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 |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Dell Children's Medical Group | Austin | Texas | 78723 | United States |
| The University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| University of Utah / Primary Children's Medical Center | Salt Lake City | Utah | 84132 | United States |
| University of Washington Medical Center | Seattle | Washington | 98195 | United States |
| University of Wisconsin Hospital and Clinics | Madison | Wisconsin | 53792 | United States |
| The Prince Charles Hospital | Chermside | Australia |
| Alfred Hospital | Melbourne, VIC | Australia |
| Perth Children's Hospital | Nedlands | Australia |
| The Royal Children's Hospital | Parkville, VIC | Australia |
| Mater Adult Hospital | South Brisbane | Australia |
| Queensland Children's Hospital | South Brisbane | Australia |
| Westmead Hospital | Westmead | Australia |
| Cliniques Universitaires de Bruxelles Hopital Erasme | Brussels | Belgium |
| Universitair Ziekenhuis Brussel - Campus Jette | Brussels | Belgium |
| Universitair Ziekenhuis Gent | Ghent | Belgium |
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | Belgium |
| Stollery Children's Hospital | Edmonton | Canada |
| McGill University Health Center | Québec | Canada |
| St. Michael's Hospital | Toronto | Canada |
| St. Paul's Hospital | Vancouver | Canada |
| Juliane Marie Center, Rigshospitalet | Copenhagen | Denmark |
| Centre Hospitalier Lyon Sud | Benite Cedex | France |
| Groupe Hospitaler Pellegrin, CHU De Bordeaux | Bordeaux | France |
| CHRU de Lille - Hopital Albert Calmette | Lille | France |
| CHU Marseille - Hopital Nord | Marseille | France |
| CHU de Montpellier - Hopital Arnaud de Villeneuve | Montpellier | France |
| Hopital Cochin | Paris | France |
| Hopital Necker, Enfants Malades | Paris | France |
| Hopital Pontchaillou CHU de Rennes | Rennes | France |
| Charite Paediatric Pulmonology Department | Berlin | Germany |
| Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital | Erlangen | Germany |
| Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen | Essen | Germany |
| Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin | Giessen | Germany |
| Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie | Halle | Germany |
| Pneumologisches Studienzentrum Muenchen-West | München | Germany |
| University Hospital Wuerzburg | Würzburg | Germany |
| Cork University Hospital | Cork | Ireland |
| Beaumont Hospital | Dublin | Ireland |
| St. Vincent's University Hospital | Dublin | Ireland |
| University Hospital Limerick (Adults) | Limerick | Israel |
| Azienda Ospedaliero Universitaria Ospedale Riuniti | Ancona | Italy |
| IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico | Genova | Italy |
| Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico | Milan | Italy |
| Malattie Apparato Respiratorio 2 - Fibrosi Cistica | Orbassano | Italy |
| Ospedale Pediatrico Bambino Gesu | Rome | Italy |
| Azienda Ospedaliera di Verona-Ospedale Civile Maggiore | Verona | Italy |
| University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis | Heidelberglaan | Netherlands |
| UMC St. Radboud | Nijmegen | Netherlands |
| HagaZiekenhuis van den Haag | The Hague | Netherlands |
| Hospital Universitari Vall d´Hebron Servicio de Broncoscopia | Barcelona | Spain |
| Hospital Virgen de la Arrixaca | Murcia | Spain |
| Hospital Universitario Virgen del Rocio | Seville | Spain |
| Hospital Universitario y Politecnico La Fe | Valencia | Spain |
| Papworth Hospital NHS Foundation Trust, Papworth Everard | Cambridge | 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 |
| 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 |
| Southampton General Hospital | Southampton | United Kingdom |
Following an IVA or 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 8 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Control: IVA or TEZ/IVA | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| BG001 | TC: ELX/TEZ/IVA | Following an IVA or 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 8 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 |
| ||||||||||||||||
| 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 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group | 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 have the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in the treatment period. This outcome measure was applicable only for the triple combination arm. | Posted | Least Squares Mean | 95% Confidence Interval | percentage points | From Baseline Through Week 8 |
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| Secondary | Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group | Sweat samples were collected using an approved collection device. | FAS. This outcome measure was applicable only for the triple combination group. | Posted | Least Squares Mean | 95% Confidence Interval | millimole per Liter (mmol/L) | From Baseline Through Week 8 |
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| Secondary | Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | FAS. | Posted | Least Squares Mean | 95% Confidence Interval | percentage points | From Baseline Through Week 8 |
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| Secondary | Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group | Sweat samples were collected using an approved collection device. | FAS. | Posted | Least Squares Mean | 95% Confidence Interval | mmol/L | From Baseline Through Week 8 |
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| Secondary | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group | 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. This outcome measure was applicable only for the triple combination arm. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | From Baseline Through Week 8 |
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| Secondary | Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group | 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 | 95% Confidence Interval | units on a scale | From Baseline Through Week 8 |
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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 | Day 1 up to Week 12 |
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Day 1 up to Week 12
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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 | Control: IVA or TEZ/IVA | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | 0 | 126 | 11 | 126 | 47 | 126 |
| EG001 | TC: ELX/TEZ/IVA | Following an IVA or 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 8 weeks. | 0 | 132 | 5 | 132 | 35 | 132 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperparathyroidism primary | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | 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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| Pneumonia | Infections and infestations | 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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| 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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| Nausea | 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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| 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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| 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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| Sputum increased | Respiratory, thoracic and mediastinal 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 | Jun 22, 2020 | May 7, 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 |
| 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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| Not Collected per Local Regulations |
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| Aboriginal |
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| Latin-American |
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| Lebanese |
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| White |
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| White, American Indian or Alaska Native |
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