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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00909727




Registration number
NCT00909727
Ethics application status
Date submitted
26/05/2009
Date registered
26/05/2009
Date last updated
18/07/2012

Titles & IDs
Public title
Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation
Scientific title
A Phase 3, 2-Part, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Pharmacokinetics, Efficacy and Safety of VX-770 in Subjects Aged 6 to 11 Years With Cystic Fibrosis and the G551D Mutation
Secondary ID [1] 0 0
VX08-770-103
Universal Trial Number (UTN)
Trial acronym
ENVISION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Cystic Fibrosis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ivacaftor
Treatment: Drugs - Placebo
Treatment: Drugs - Ivacaftor
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.

Experimental: 150 mg Ivacaftor q12h - Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.

Placebo Comparator: Placebo - Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.

Experimental: 150 mg Ivacaftor q12h - Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.


Treatment: Drugs: Ivacaftor
150-mg tablet given orally q12h for up to 48 weeks

Treatment: Drugs: Placebo
Tablet given orally q12h for up to 48 weeks

Treatment: Drugs: Ivacaftor
150-mg tablet given orally q12h for up to 48 weeks

Treatment: Drugs: Placebo
Tablet given orally q12h for up to 48 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 - Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Timepoint [1] 0 0
baseline through 24 weeks
Primary outcome [2] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 - Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Timepoint [2] 0 0
baseline through 24 weeks
Secondary outcome [1] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 - Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Timepoint [1] 0 0
baseline through 48 weeks
Secondary outcome [2] 0 0
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children) - The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).
Timepoint [2] 0 0
baseline through 24 weeks and 48 weeks
Secondary outcome [3] 0 0
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 - The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
Timepoint [3] 0 0
baseline through 24 weeks and 48 weeks
Secondary outcome [4] 0 0
Absolute Change From Baseline in Weight at Week 24 and Week 48 - As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.
Timepoint [4] 0 0
baseline to 24 weeks and 48 weeks
Secondary outcome [5] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 - Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Timepoint [5] 0 0
baseline through 48 weeks
Secondary outcome [6] 0 0
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children) - The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).
Timepoint [6] 0 0
baseline through 24 weeks and 48 weeks
Secondary outcome [7] 0 0
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 - The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
Timepoint [7] 0 0
baseline through 24 weeks and 48 weeks
Secondary outcome [8] 0 0
Absolute Change From Baseline in Weight at Week 24 and Week 48 - As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.
Timepoint [8] 0 0
baseline to 24 weeks and 48 weeks

Eligibility
Key inclusion criteria
- Weighing at least 15 kg

- Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele

- Forced expiratory volume in 1 second (FEV1) of 40% to 105% (inclusive) of predicted
normal for age, gender, and height (Knudson standards) at Screening

- Able to swallow tablets

- As judged by the investigator, parent or legal guardian and subject must have been
able to understand protocol requirements, restrictions, and instructions, and the
parent or legal guardian should have been able to ensure that the subject complied
with, and was likely to complete, the study as planned

- Parent or legal guardian must have signed the informed consent form and corresponding
assent must be obtained from the subject

- Willing to use at least 1 highly effective birth control method during the study

- No clinically significant abnormalities that would have interfered with the study
assessments, as judged by the investigator
Minimum age
6 Years
Maximum age
11 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of any illness or condition that might confound the results of the study or
pose an additional risk in administering study drug to the subject

- Acute respiratory infection, pulmonary exacerbation, or changes in therapy for
pulmonary disease within 4 weeks of Day 1 of the study

- Abnormal liver function = 3x the upper limit of normal

- Abnormal renal function at Screening

- History of solid organ or hematological transplantation

- Ongoing participation in another therapeutic clinical study or prior participation in
an investigational drug study within 30 days prior to Screening

- Use of inhaled hypertonic saline treatment

- Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital Brisbane - Herston
Recruitment hospital [3] 0 0
Royal Children's Hospital Melbourne - Parkville
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
Germany
State/province [17] 0 0
Erlangen
Country [18] 0 0
Germany
State/province [18] 0 0
Jena
Country [19] 0 0
Ireland
State/province [19] 0 0
Dublin
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cystic Fibrosis Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cystic Fibrosis Foundation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects
with cystic fibrosis aged 6 to 11 years who have the G551D mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective
potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators
are pharmacological agents that increase the chloride ion transport properties of the channel
in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA)
activation.
Trial website
https://clinicaltrials.gov/show/NCT00909727
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Ahrens, MD
Address 0 0
Roy A. & Lucille A. Carver College of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications