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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-004479-35 | EudraCT Number |
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This study will evaluate the efficacy of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 through 11 years, who are homozygous for the F508del mutation (F/F) or heterozygous for F508del with an eligible residual function mutation (F/RF).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Other | Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. |
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| TEZ/IVA | Experimental | Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks. |
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| Ivacaftor | Experimental | Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TEZ/IVA | Drug | Participants weighing <40 kg received TEZ 50 mg/IVA 75 mg FDC tablet and those weighing ≥40 kg received TEZ 100 mg/IVA 150 mg FDC tablet. |
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| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Through Week 8 | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | From baseline through Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Sweat Chloride At Week 8 | Sweat samples were collected using an approved collection device. | From baseline at Week 8 |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 |
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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 |
|---|---|---|---|---|---|---|
| Hunter Medical Research Institute (HMRI) | New Lambton Heights | Australia | ||||
| Princess Margaret Hospital for Children |
| 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. | |
| 33331662 | Derived |
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A total of 69 participants were randomized, out of which 67 participants received study drug and were included in participant flow and baseline characteristics section.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. |
| FG001 | 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 | Nov 17, 2017 | Nov 28, 2019 |
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| IVA | Drug | Participants weighing <40 kg IVA 75 mg tablet and those weighing ≥40 kg received IVA 150 mg tablet. |
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| Placebo | Drug | Placebo matched to TEZ/IVA FDC |
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| Placebo | Drug | Placebo matched to IVA |
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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 through Week 8 |
| Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit | From first dose of study drug up to safety follow-up visit (up to Week 12) |
| Perth |
| Australia |
| Lady Cilento Children's Hospital | South Brisbane | Australia |
| The Children's Hospital at Westmead | Westmead | Australia |
| Universitair Ziekenhuis Brussel - Campus Jette | Brussels | Belgium |
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | Belgium |
| University of Copenhagen Rigshospitalet | Copenhagen | Denmark |
| Groupe Hospitalier Pellegrin - Hôpital des Enfants | Bordeaux | France |
| Hôpital Necker - Enfants Malades | Paris | France |
| Universitaetsklinikum Koeln | Cologne | Germany |
| Universitaetsklinikum Essen | Essen | Germany |
| Klinikum der Johann Wolfgang Goethe-Universitaet | Frankfurt | Germany |
| Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen | Giessen | Germany |
| Medizinische Hochschule Hannover | Hanover | Germany |
| Universitaetsklinikum Heidelberg | Heidelberg | Germany |
| Universitaetsklinikum Jena | Jena | Germany |
| Universitaetsklinikum Tuebingen | Tübingen | Germany |
| Our Lady's Children's Hospital | Dublin | Ireland |
| University Hospital Limerick | Limerick | Ireland |
| Klinika Mukowiscydozy, Oddział Chorób Płuc SZP ZOZ | Dziekanów Leśny | Poland |
| Inselspital - Universitaetsspital Bern | Bern | Switzerland |
| Kinderspital Zuerich | Zurich | Switzerland |
| Royal Hospital for Sick Children | Edinburgh | United Kingdom |
| Leeds General Infirmary | Leeds | United Kingdom |
| Royal Brompton Hospital | London | United Kingdom |
| Nottingham University Hospital City Campus | Nottingham | United Kingdom |
| Southampton General Hospital | Southampton | United Kingdom |
| 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. |
Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.
| FG002 | Ivacaftor | Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. |
| BG001 | TEZ/IVA | Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks. |
| BG002 | Ivacaftor | Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. |
| BG003 | 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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| Lung Clearance Index 2.5 (LCI2.5) | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | Mean | Standard Deviation | lung clearance index |
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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 Lung Clearance Index 2.5 (LCI2.5) Through Week 8 | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | Full Analysis Set: all participants who were randomized, received at least 1 dose of study drug and had an eligible genotype. As per the pre-specified analysis, efficacy was only planned to be assessed for TEZ/IVA group. Placebo or IVA groups were used for blinding purposes only and were not applicable for the purpose of primary efficacy analysis. | Posted | Least Squares Mean | Standard Error | lung clearance index | From baseline through Week 8 |
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| Secondary | Absolute Change in Sweat Chloride At Week 8 | Sweat samples were collected using an approved collection device. | FAS. As per the pre-specified analysis, efficacy was only planned to be assessed for TEZ/IVA group. Placebo or IVA groups were used for blinding purposes only and were not applicable for the purpose of secondary efficacy analysis. | Posted | Least Squares Mean | Standard Error | millimole per liter (mmol/L) | From baseline at Week 8 |
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| Secondary | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score 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. | FAS. As per the pre-specified analysis, efficacy was only planned to be assessed for TEZ/IVA group. Placebo or IVA groups were used for blinding purposes only and were not applicable for the purpose of secondary efficacy analysis. | Posted | Least Squares Mean | Standard Error | units on a scale | From baseline through Week 8 |
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| Secondary | Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit | Safety set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From first dose of study drug up to safety follow-up visit (up to Week 12) |
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From first dose of study drug up to safety follow-up visit (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 | Placebo | Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. | 0 | 10 | 0 | 10 | 8 | 10 |
| EG001 | TEZ/IVA | Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks. | 0 | 54 | 0 | 54 | 31 | 54 |
| EG002 | Ivacaftor | Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. | 0 | 3 | 0 | 3 | 2 | 3 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | 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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| Cough | 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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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Productive cough | 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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| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Blister | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | 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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| Gastroenteritis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Bacterial disease carrier | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Impetigo | 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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| Viral upper respiratory tract infection | Infections and infestations | 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 | Oct 31, 2018 | Nov 28, 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 |
|---|---|
| C000625213 | tezacaftor |
| 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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| 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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