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Cystic FibrosisPhase 2DISCOVERNCT00953706

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation

A Phase 2 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 34 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Read more about this study

Who is it for?
Ages 12 years and older
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
140 participants
Where
34 sitesUnited States
Study dates
Sep 2009to May 2013
Phase
Phase 2
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation
  • Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
  • Willing to use at least 2 highly effective birth control methods during the study
  • No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
  • Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, 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
  • History of alcohol, medication or illicit drug abuse within one year prior to Day 1
  • Abnormal liver function >=3 x the upper limit of normal
  • Abnormal renal function at Screening
  • History of solid organ or hematological transplantation
Show all 11Show fewer
  • Pregnant or breast-feeding (for women)
  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening
  • Previous participation in a VX-809 study
  • Used inhaled hypertonic saline treatment
  • Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

United States34 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308

  • Albany Medical College

    Albany, New York, 12208

  • Providence Medical Center

    Anchorage, Alaska, 99508

  • University of Alabama

    Birmingham, Alabama, 35294

  • St. Luke's CF clinic

    Boise, Idaho, 83712

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Women and Children's Hospital of Buffalo

    Buffalo, New York, 14222

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Chicago

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Vermont Lung Center at the University of Vermont

    Colchester, Vermont, 05446

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Helen DeVos Children's Hospital; Spectrum Health Hospitals

    Grand Rapids, Michigan, 49503

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • New York Medical College

    Hawthorne, New York, 10532

  • Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • The Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740

  • University of Tennessee

    Memphis, Tennessee, 38103

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Morristown Memorial Hospital

    Morristown, New Jersey, 07962

  • The CF Center, Beth Israel Medical Center

    New York, New York, 10003

  • Columbia University Medical Center

    New York, New York, 10032

  • Kaiser Permanente Medical Care Program

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nemours Children's Clinic

    Orlando, Florida, 32801

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Maine Medical Center

    Portland, Maine, 04102

  • Medical College of Virginia

    Richmond, Virginia, 23298

  • Univeristy of Utah

    Salt Lake City, Utah, 84132

  • Toldedo Children's Hospital

    Toledo, Ohio, 43606

  • University of Massachussetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Ivacaftor is a potent and selective CFTR 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 study investigated the effects of ivacaftor in participants with cystic fibrosis (CF) >=12 years of age with a forced expiratory volume in 1 second (FEV1) >=40 percent (%) predicted. This study was conducted in 2 parts.

  • Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of participants with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation.
  • Part B of this study was an open-label extension of Part A, enrolling participants who completed Part A and met pre-specified endpoint criteria, and explored the safety and efficacy of ivacaftor over long-term treatment in participants with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.
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

    Tablet

  • PlaceboDrug

    Tablet

Study groups in NCT00953706
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Receives: Drug: Ivacaftor; Drug: Placebo
IvacaftorExperimentalIvacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Receives: Drug: Ivacaftor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16

    Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.

    Measured: Part A baseline through Week 16

Secondary outcomes (12)

  1. Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16

    The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

    Measured: Part A baseline through Week 16

  2. Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16

    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: Part A baseline through Week 16

  3. Part A : Rate of Change From Baseline in Weight Through Week 16

    As malnutrition is common in participants 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: Part A baseline through Week 16

  4. Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64

    ppFEV1 is defined in Outcome Measure 1.

    Measured: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

  5. Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64

    ppFEV1 is defined in Outcome Measure 1.

    Measured: Part A baseline through Week 64

  6. Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64

    ppFEV1 is defined in Outcome Measure 1.

    Measured: Part B baseline through Week 64

  7. Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64

    The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

    Measured: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

  8. Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64

    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: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

  9. Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64

    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: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

  10. Part B : Number of Participants With Pulmonary Exacerbations

    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    Measured: Part B baseline through Week 64

  11. Part B : Number of Pulmonary Exacerbation Events

    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    Measured: Part B baseline through Week 64

  12. Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year

    Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    Measured: Part B baseline through Week 64

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJul 2010
  4. Study completionMay 2013

Why it stopped: Following review of results obtained from a pre-specified 6-month analysis of Part B data the study was terminated on the basis of futility.

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00953706
Sponsor's protocol ID
VX08-770-104
Other IDs
2009-010261-23, 2009
Acronym
DISCOVER
Status last verified
Aug 2015
First submitted
4 Aug 2009
Last updated
11 Sep 2015
Data monitoring committee
Yes

Publications

  • Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordonez CL, Geller DE; VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672.

    PubMed 22383668

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 34 sites in United States.

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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 11 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 (time frame: Part A baseline through Week 16). 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 NCT00953706, 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 11 Sep 2015.

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