Cystic FibrosisPhase 3ENVISIONNCT00909727
Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation
A Phase 3 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 29 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 11 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Ivacaftor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 29 sitesin 7 countries
- Study dates
- Aug 2009to Apr 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
United States17 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory Cystic Fibrosis Center
Atlanta, Georgia, 30322
University of Alabama
Birmingham, Alabama, 35233-1711
Massachusetts General Hospital
Boston, Massachusetts, 02114
Children's Hospital Boston
Boston, Massachusetts, 02115
University of Virginia Pediatric Respiratory Medicine
Charlottesville, Virginia, 22908
Children's Memorial Hospital
Chicago, Illinois, 60614
Children's Hospital of Michigan
Detroit, Michigan, 48201
The Cystic Fibrosis Center of Chicago
Glenview, Illinois, 60025
Helen DeVos Children's Hospital Spectrum Health Hospitals
Grand Rapids, Michigan, 49503
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Iowa Department of Pediatrics
Iowa City, Iowa, 52242
The Children's Mercy Hospital
Kansas City, Missouri, 64108
East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care
Knoxville, Tennessee, 37916
University of Minnesota
Minneapolis, Minnesota, 55455
University of Nebraska Medical Center Pediatric Pulmonary/ CF
Omaha, Nebraska, 68195-5190
University of Utah Pediatric Pulmonology
Salt Lake City, Utah, 84108
Australia4 sites
Royal Children's Hospital Brisbane
Herston, Queensland, 4029
Royal Children's Hospital Melbourne
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Subiaco, Western Australia, 6008
The Children's Hospital Westmead
Westmead, New South Wales, 2145
Canada2 sites
Hospital for Sick Children CF Center
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H-3V4
Germany2 sites
Kinder- und Jugendklinik Universitätsklinikum Erlangen
Erlangen, 91054
Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
Jena, 07740
Ireland2 sites
Our Lady's Children's Hospital
Dublin, 12
The National Children's Hospital
Dublin, 24
France1 site
Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition
Paris, 75935
United Kingdom1 site
Dept of Gene Therapy, Imperial College London
London, SW3 6LR
About this study
Official 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
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.
Read the detailed description
This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards).
Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.
This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.
- Conditions
- Cystic Fibrosis
- Being tested
- Ivacaftor, Placebo
- Keywords
- Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Pathologic Processes
- Medical subject headings
- Cystic Fibrosis, Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvacaftorDrug
Also called VX-770
150-mg tablet given orally q12h for up to 48 weeks
PlaceboDrug
Tablet given orally q12h for up to 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects who received placebo every 12 hours (q12h) for up to 48 weeks. Receives: Drug: Placebo |
| 150 mg Ivacaftor q12h | Experimental | Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks. Receives: Drug: Ivacaftor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline through 24 weeks
Secondary outcomes (4)
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.
Measured: baseline through 48 weeks
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).
Measured: baseline through 24 weeks and 48 weeks
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.
Measured: baseline through 24 weeks and 48 weeks
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.
Measured: baseline to 24 weeks and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2009 (estimated)
- Study startAug 2009
- Primary completionNov 2010
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Richard Ahrens, MD, Principal investigator, Roy A. & Lucille A. Carver College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00909727
- Sponsor's protocol ID
- VX08-770-103
- Acronym
- ENVISION
- Status last verified
- Jul 2012
- First submitted
- 26 May 2009
- Last updated
- 21 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, Mainz JG, Rodriguez S, Li H, Yen K, Ordonez CL, Ahrens R; VX08-770-103 (ENVISION) Study Group. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013 Jun 1;187(11):1219-25. doi: 10.1164/rccm.201301-0153OC.
PubMed 23590265
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00909727
- Acronym / sponsor ID
- ENVISION / VX08-770-103
- Conditions
- Cystic Fibrosis
- Keywords
- Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Pathologic Processes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- Aug 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 28 May 2009 (estimated)
- Results
- Posted 21 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards).
Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.
This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects who received placebo every 12 hours (q12h) for up to 48 weeks. |
| 150 mg Ivacaftor q12h | Experimental | Drug: IvacaftorSubjects who received 150 mg of ivacaftor q12h for up to 48 weeks. |
Who may qualify
- Ages
- 6 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvacaftorAlso: VX-770150-mg tablet given orally q12h for up to 48 weeks | Drug | 150 mg Ivacaftor q12h |
| PlaceboTablet given orally q12h for up to 48 weeks | Drug | Placebo |
Primary outcome
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Time frame: baseline through 24 weeks
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
4 secondary outcomes
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48
Time frame: baseline through 48 weeks
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)
Time frame: baseline through 24 weeks and 48 weeks
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48
Time frame: baseline through 24 weeks and 48 weeks
Absolute Change From Baseline in Weight at Week 24 and Week 48
Time frame: baseline to 24 weeks and 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23590265Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, Mainz JG, Rodriguez S, Li H, Yen K, Ordonez CL, Ahrens R; VX08-770-103 (ENVISION) Study Group. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013 Jun 1;187(11):1219-25. doi: 10.1164/rccm.201301-0153OC.
- Genetics Home ReferenceLink provided by the sponsor.
- Medline PlusLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Ahrens, MD principal investigator
Roy A. & Lucille A. Carver College of Medicine
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 29 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, Canada, Germany, Ireland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 (time frame: baseline through 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00909727, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2012.