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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03691779
Registration number
NCT03691779
Ethics application status
Date submitted
28/09/2018
Date registered
2/10/2018
Date last updated
22/10/2021
Titles & IDs
Public title
Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age
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Scientific title
A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age
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Secondary ID [1]
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2018-001695-38
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Secondary ID [2]
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VX18-445-106
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Cystic fibrosis
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Respiratory
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Other respiratory disorders / diseases
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Inflammatory and Immune System
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Connective tissue diseases
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - ELX/TEZ/IVA
Treatment: Drugs - IVA
Experimental: Part A: ELX/TEZ/IVA - Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.
Experimental: Part B: ELX/TEZ/IVA - Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Treatment: Drugs: ELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.
Treatment: Drugs: IVA
IVA tablet orally once daily in the evening.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
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Assessment method [1]
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Timepoint [1]
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Part A: Day 15
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Primary outcome [2]
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Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA
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Assessment method [2]
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Timepoint [2]
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Part A: Day 15
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Primary outcome [3]
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Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA
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Assessment method [3]
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Timepoint [3]
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Part A: Day 15
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Primary outcome [4]
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Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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Assessment method [4]
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Timepoint [4]
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Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
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Secondary outcome [1]
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Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
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Assessment method [1]
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Timepoint [1]
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Part A: Day 15
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Secondary outcome [2]
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Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
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Assessment method [2]
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Timepoint [2]
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Part A: Day 15
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Secondary outcome [3]
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Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)
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Assessment method [3]
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Timepoint [3]
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Part A: Day 15
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Secondary outcome [4]
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Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)
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Assessment method [4]
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The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.
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Timepoint [4]
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Part A: Day 15
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Secondary outcome [5]
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Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs
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Assessment method [5]
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Timepoint [5]
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Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)
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Secondary outcome [6]
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Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
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Assessment method [6]
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FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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Timepoint [6]
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Part B: From Baseline Through Week 24
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Secondary outcome [7]
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Part B: Absolute Change in Sweat Chloride (SwCl)
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Assessment method [7]
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Sweat samples were collected using an approved collection device.
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Timepoint [7]
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Part B: From Baseline Through Week 24
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Secondary outcome [8]
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Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
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Assessment method [8]
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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.
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Timepoint [8]
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Part B: From Baseline Through Week 24
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Secondary outcome [9]
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Part B: Absolute Change in Body Mass Index (BMI)
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Assessment method [9]
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BMI was defined as weight in kg divided by squared height in meters (m\^2).
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Timepoint [9]
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Part B: From Baseline at Week 24
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Secondary outcome [10]
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Part B: Absolute Change in BMI For-Age Z-Score
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Assessment method [10]
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BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
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Timepoint [10]
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Part B: From Baseline at Week 24
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Secondary outcome [11]
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Part B: Absolute Change in Weight
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Assessment method [11]
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Timepoint [11]
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Part B: From Baseline at Week 24
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Secondary outcome [12]
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Part B: Absolute Change in Weight-for-age Z-Score
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Assessment method [12]
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The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
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Timepoint [12]
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Part B: From Baseline at Week 24
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Secondary outcome [13]
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Part B: Absolute Change in Height
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Assessment method [13]
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Timepoint [13]
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Part B: From Baseline at Week 24
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Secondary outcome [14]
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Part B: Absolute Change in Height-for-Age Z-Score
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Assessment method [14]
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The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
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Timepoint [14]
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Part B: From Baseline at Week 24
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Secondary outcome [15]
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Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale
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Assessment method [15]
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The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.
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Timepoint [15]
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Part B: At Week 24
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Secondary outcome [16]
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Part B: Number of Pulmonary Exacerbations Events
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Assessment method [16]
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Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.
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Timepoint [16]
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Part B: From Baseline Through Week 24
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Secondary outcome [17]
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Part B: Number of CF Related Hospitalizations
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Assessment method [17]
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The total number of CF related hospitalization events across all participants were reported.
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Timepoint [17]
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Part B: From Baseline Through Week 24
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Secondary outcome [18]
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Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)
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Assessment method [18]
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Timepoint [18]
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Part B: At Week 4
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Secondary outcome [19]
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Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)
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Assessment method [19]
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LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
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Timepoint [19]
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Part B: From Baseline Through Week 24
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Eligibility
Key inclusion criteria
Key
* Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
* Forced expiratory volume in 1 second (FEV1) value =40% of predicted mean for age, sex, and height.
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Minimum age
6
Years
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Maximum age
11
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status.
* Solid organ or hematological transplantation.
Other protocol defined Inclusion/Exclusion criteria may apply.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/10/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
7/08/2020
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Sample size
Target
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Accrual to date
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Final
71
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Queensland Children's Hospital - South Brisbane
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Recruitment hospital [2]
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The Children's Hospital at Westmead - Westmead
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Recruitment postcode(s) [1]
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- South Brisbane
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Recruitment postcode(s) [2]
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- Westmead
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Recruitment outside Australia
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United States of America
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State/province [1]
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California
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United States of America
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Colorado
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United States of America
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Illinois
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Massachusetts
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Oregon
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Texas
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Washington
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Canada
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Toronto
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Country [14]
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Canada
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State/province [14]
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Vancouver
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Country [15]
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Ireland
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State/province [15]
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Dublin
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United Kingdom
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Birmingham
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United Kingdom
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State/province [17]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Vertex Pharmaceuticals Incorporated
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.
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Trial website
https://clinicaltrials.gov/study/NCT03691779
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Trial related presentations / publications
Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA. A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2021 Jun 15;203(12):1522-1532. doi: 10.1164/rccm.202102-0509OC. 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.
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Public notes
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Contacts
Principal investigator
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/79/NCT03691779/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/79/NCT03691779/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03691779
Download to PDF