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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004794-13 | EudraCT Number |
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This study will evaluate the safety and pharmacokinetics (PK) of lumacaftor (LUM) and ivacaftor (IVA) in participants 1 to less than 2 years of age with cystic fibrosis (CF), homozygous for F508del (F/F).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: LUM/IVA | Experimental | Participants weighing 7 to less than (<)10 kilograms (kg) at screening received LUM 75 milligrams (mg)/IVA 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. |
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| Part B: LUM/IVA | Experimental | Participants weighing 7 to <9 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LUM | Drug | Fixed Dose Combination (FDC) granules (LUM/IVA). |
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| Measure | Description | Time Frame |
|---|---|---|
| Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Day 1 and Day 15 | |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | Pre-dose at Day 8 and Day 15 | |
| Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Day 25 | |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) |
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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 | ||
| Arkansas Children's Hospital |
| 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. | |
| 35771568 | 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 participants with cystic fibrosis (CF) aged 1 through less than 2 years of age who are homozygous for F508del. A total of 61 participants were enrolled in Parts A and B of the study. One participant in Part B was enrolled but not dosed in this study. Therefore, data for 60 participants are reported in the participant flow and baseline characteristics sections.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: LUM/IVA | Participants weighing 7 to less than( <)10 kilograms (kg) at screening received lumacaftor (LUM) 75 milligrams (mg)/ ivacaftor (IVA) 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. |
| 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 29, 2020 | Oct 28, 2022 |
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| IVA | Drug | FDC granules (LUM/IVA). |
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| Pre-dose at Day 8 and Day 15 |
| Part B: Absolute Change in Sweat Chloride | From Baseline at Week 24 |
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | Pre-dose at Day 15, Week 4, Week 12 and Week 24 |
| Little Rock |
| Arkansas |
| 72202 |
| United States |
| Stanford University | Palo Alto | California | 94304 | United States |
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| Yale New Haven Medical Center | New Haven | Connecticut | 06511 | United States |
| Nemours / Alfred I. duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30329 | United States |
| Ann & Robert Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Riley Hospital for Children at Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota | Minneapolis | Minnesota | 55404 | United States |
| The Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Cardinal Glennon Children's Hospital - St. Louis University | St Louis | Missouri | 63104 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| University of North Carolina Hospitals | Chapel Hill | North Carolina | 27514 | United States |
| Wake Forest University School of Medicine - Brenner Children's Hospital | Winston-Salem | North Carolina | 27157 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Medical Center of Dallas | Dallas | Texas | 75235 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| University of Utah / Primary Children's Medical Center | Salt Lake City | Utah | 84132 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| University of Wisconsin Hospital and Clinics | Madison | Wisconsin | 53792 | United States |
| McGill University Health Centre, Glen Site, Montreal Children's Hospital | Montreal | Canada |
| The Hospital for Sick Children | Toronto | Canada |
| British Columbia's Children's Hospital | Vancouver | Canada |
| Rayment JH, Asfour F, Rosenfeld M, Higgins M, Liu L, Mascia M, Paz-Diaz H, Tian S, Zahigian R, McColley SA. A Phase 3, Open-Label Study of Lumacaftor/Ivacaftor in Children 1 to Less Than 2 Years of Age with Cystic Fibrosis Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2022 Nov 15;206(10):1239-1247. doi: 10.1164/rccm.202204-0734OC. |
| 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. |
| FG001 | Part B: LUM/IVA | Participants weighing 7 to <9 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. |
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| NOT COMPLETED |
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All participants who received at least one dose of the study drug during the treatment period were included in the baseline analysis. The baseline analysis was collected for the overall treatment arm, irrespective of a weight-based dose regimen. Therefore, the analysis is reported in a single arm for each study part (Part A: LUM/IVA and Part B: LUM/IVA).
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A: LUM/IVA | Participants weighing 7 to less than(<)10 kilograms (kg) at screening received lumacaftor (LUM) 75 milligrams (mg)/ ivacaftor (IVA) 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. |
| BG001 | Part B: LUM/IVA | Participants weighing 7 to <9 kg at screening received LUM 75 mg/ IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. |
| 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, Categorical | Count of Participants | Participants |
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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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| 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 | Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA | Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Day 1 and Day 15 |
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| Primary | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA | PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose at Day 8 and Day 15 |
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| Primary | Part B : 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. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm. | Posted | Number | participants | From Day 1 up to Week 26 |
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| Secondary | Part A: 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. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part A: LUM/IVA arm. | Posted | Number | participants | From Day 1 up to Day 25 |
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| Secondary | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose at Day 8 and Day 15 |
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| Secondary | Part B: Absolute Change in Sweat Chloride | The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B.The pharmacodynamic analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm. | Posted | Mean | Standard Deviation | Millimole per liter (mmol/L) | From Baseline at Week 24 |
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| Secondary | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA) | PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose at Day 15, Week 4, Week 12 and Week 24 |
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From Day 1 Through Safety Follow-up Period (up to Day 25 for Part A and up to Week 26 for Part B)
The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single arm for each study part (Part A: LUM/IVA and Part B: LUM/IVA).
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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 | Part A: LUM/IVA | Participants weighing 7 to <10 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. | 0 | 14 | 0 | 14 | 12 | 14 |
| EG001 | Part B: LUM/IVA | Participants weighing 7 to <9 kg at screening received LUM 75 mg/ IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg FDC q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. | 0 | 46 | 5 | 46 | 42 | 46 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post procedural fever | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
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| Distal intestinal obstruction syndrome | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lip injury | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
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| Pseudomonas test positive | Investigations | MedDRA (24.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Crying | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | 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 | May 19, 2021 | Oct 28, 2022 | SAP_001.pdf |
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| 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 |
|---|---|
| C569105 | lumacaftor |
| C545203 | ivacaftor |
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| >=65 years |
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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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| Black or African American |
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| Asian |
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| American Indian or Alaska Native |
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| Native Hawaiian or Other Pacific Islander |
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| Not collected per local regulations |
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| Other |
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| Day 15: LUM |
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| Day 1: IVA |
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| Day 15: IVA |
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