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CompletedNCT00909727ENVISIONUpdated Aug 21, 2012Results posted

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation

A Phase 3 interventional study of Ivacaftor and Placebo in Cystic Fibrosis, sponsored by Vertex Pharmaceuticals Incorporated. Completed at 29 sites in 7 countries. Open to participants aged 6 Years to 11 Years. Per ClinicalTrials.gov, last updated 2012-08-21.

Sponsored by Vertex Pharmaceuticals Incorporated · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
6 Years to 11 Years
Sex
All
01

Study 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.

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.

02

Conditions studied

  • Cystic Fibrosis

Keywords

  • Fibrosis
  • Pancreatic Diseases
  • Digestive System Diseases
  • Lung Diseases
  • Respiratory Tract Diseases
  • Genetic Diseases, Inborn
  • Infant, Newborn, Diseases
  • Pathologic Processes
03

In context

Cystic Fibrosis

1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.

This study's enrollment of 52 is above the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.

Browse Cystic Fibrosis studies →

Lead sponsor

Vertex Pharmaceuticals Incorporated is the lead sponsor of 243 studies on the registry; 19 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 49 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 11 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion criteria

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)
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
52 participants (actual)

Study arms

  • Placebo comparator
    Placebo

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

    Drug: Placebo

  • Experimental
    150 mg Ivacaftor q12h

    Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.

    Drug: Ivacaftor

Interventions

  • DrugIvacaftor

    150-mg tablet given orally q12h for up to 48 weeks

    Also known as: VX-770

  • DrugPlacebo

    Tablet given orally q12h for up to 48 weeks

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: baseline through 24 weeks

Secondary outcomes

  1. 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.

    Time frame: baseline through 48 weeks

  2. 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).

    Time frame: baseline through 24 weeks and 48 weeks

  3. 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.

    Time frame: baseline through 24 weeks and 48 weeks

  4. 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.

    Time frame: baseline to 24 weeks and 48 weeks

07

Results

Posted Aug 21, 2012

Participant flow

Part A started on 05 August 2009 (signing of first informed consent). Screening evaluations were completed during Day -28 to Day -2. All subjects completing Part A were offered the opportunity to participate in Part B, which started on 12 March 2010. Screening evaluations were completed during Day -35 to Day -15 before the first dose of study drug.

Participant flow — Overall Study
MilestonePlacebo150 mg Ivacaftor q12h
Started2626
Completed treatment period, week 242326
Completed2226
Not completed40
Withdrew: Adverse event10
Withdrew: Wrong genotype10
Withdrew: Withdrawal of consent10
Withdrew: Prohibited medication10

Outcome measures

PrimaryAbsolute 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.

Time frame:
baseline through 24 weeks
Reported as:
Least squares mean · percent of predicted volume (L)
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
percent of predicted volume (L)Placebo150 mg Ivacaftor q12h
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 240.1 ± 2.112.6 ± 2.1
Statistical analysis
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = <0.0001 (The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).) · Mean difference (final values): 12.5 · 95% CI 6.6 to 18.3Denominator degrees of freedom were estimated using the Kenward-Roger approximation. No imputation of missing data was done.
SecondaryAbsolute 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.

Time frame:
baseline through 48 weeks
Reported as:
Least squares mean · percent of predicted volume (L)
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48
percent of predicted volume (L)Placebo150 mg Ivacaftor q12h
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 480.7 ± 2.010.7 ± 1.9
Statistical analysis
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = 0.0006 (There was no adjustment for multiple comparisons.) · Mean difference (final values): 10.0 · 95% CI 4.5 to 15.5Denominator degrees of freedom were estimated using the Kenward-Roger approximation. no imputation of missing data was done.
SecondaryAbsolute 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).

Time frame:
baseline through 24 weeks and 48 weeks
Reported as:
Least squares mean · score on a scale
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)
score on a scalePlacebo150 mg Ivacaftor q12h
Change from Baseline Through Week 240.3 ± 2.66.3 ± 2.5
Change from Baseline Through Week 481.0 ± 2.36.1 ± 2.2
Statistical analysis
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = 0.1092 (The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).) · Mean difference (final values): 6.1 · 95% CI -1.4 to 13.5
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = 0.1354 (There was no adjustment for multiple comparisons.) · Mean difference (final values): 5.1 · 95% CI -1.6 to 11.8
SecondaryAbsolute 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.

Time frame:
baseline through 24 weeks and 48 weeks
Reported as:
Least squares mean · millimoles per liter
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48
millimoles per literPlacebo150 mg Ivacaftor q12h
Change from Baseline Through Week 24-1.2 ± 2.6-55.5 ± 2.6
Change from Baseline Through Week 48-2.6 ± 2.6-56.0 ± 2.5
Statistical analysis
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = <0.0001 (The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).) · Mean difference (final values): -54.3 · 95% CI -61.8 to -46.8
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = <0.0001 (There was no adjustment for multiple comparisons.) · Mean difference (final values): -53.5 · 95% CI -60.9 to -46.0
SecondaryAbsolute 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.

Time frame:
baseline to 24 weeks and 48 weeks
Reported as:
Least squares mean · kilograms
Absolute Change From Baseline in Weight at Week 24 and Week 48
kilogramsPlacebo150 mg Ivacaftor q12h
At Week 241.8 ± 0.43.7 ± 0.4
At Week 483.1 ± 0.55.9 ± 0.5
Statistical analysis
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = 0.0004 (The primary endpoint and key secondary endpoints were tested in sequence. test 1: primary (α=0.05); test 2: using Hochberg's step-up procedure on weight (Wk 24) and sweat chloride (Wk 24)(α=0.05); test 3: CFQ-R respiratory domain score (Wk 24).) · Mean difference (final values): 1.9 · 95% CI 0.9 to 2.9
  • Placebo vs 150 mg Ivacaftor q12h · Mixed Models Analysis · p = 0.0002 (P-value is for the treatment effect at Week 48 (obtained as a linear contrast of treatment at Day 336). There was no adjustment for multiple comparisons.) · Mean difference (final values): 2.8 · 95% CI 1.3 to 4.2

Adverse events

Collected over For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—6/26 (23.1%)25/26 (96.2%)
150 mg Ivacaftor q12h—5/26 (19.2%)26/26 (100%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventPlacebo150 mg Ivacaftor q12h
Cystic fibrosis lungCongenital, familial and genetic disorders3/262/26
Productive coughRespiratory, thoracic and mediastinal disorders1/261/26
Lung consolidationRespiratory, thoracic and mediastinal disorders1/260/26
Abdominal painGastrointestinal disorders0/261/26
ConstipationGastrointestinal disorders1/260/26
Hepatic enzyme increasedInvestigations0/261/26
Pulmonary function test decreasedInvestigations1/260/26
Adjustment disorderPsychiatric disorders1/260/26
AnxietyPsychiatric disorders1/260/26
Affective disorderPsychiatric disorders1/260/26
Most frequent other events
Showing 10 of 45
Most frequent other events
EventPlacebo150 mg Ivacaftor q12h
CoughRespiratory, thoracic and mediastinal disorders19/2613/26
Oropharyngeal painRespiratory, thoracic and mediastinal disorders4/267/26
VomitingGastrointestinal disorders7/262/26
PyrexiaGeneral disorders7/266/26
Cystic fibrosis lungCongenital, familial and genetic disorders6/267/26
HeadacheNervous system disorders4/267/26
NasopharyngitisInfections and infestations2/266/26
Upper respiratory tract infectionInfections and infestations2/266/26
Abdominal pain upperGastrointestinal disorders5/266/26
Nasal congestionRespiratory, thoracic and mediastinal disorders4/265/26

Baseline characteristics

Age Continuous
Age Continuous(years)Placebo150 mg Ivacaftor q12hTotal
Mean8.9 ± 1.868.9 ± 2.008.9 ± 1.91
Age, Customized
Age, Customized(participants)Placebo150 mg Ivacaftor q12hTotal
6 to 8 Years131225
9 to 11 Years121123
> 11 Years134
Sex: Female, Male
Sex: Female, Male(Participants)Placebo150 mg Ivacaftor q12hTotal
Female101727
Male16925
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Placebo150 mg Ivacaftor q12hTotal
White232245
Other123
Not Allowed to Ask Per Local Regulations224
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Placebo150 mg Ivacaftor q12hTotal
Hispanic or Latino011
Not Hispanic or Latino242347
Not Allowed to Ask Per Local Regulations224
Region of Enrollment
Region of Enrollment(participants)Placebo150 mg Ivacaftor q12hTotal
North America151227
Europe5611
Australia6814
Weight
Weight(kilograms)Placebo150 mg Ivacaftor q12hTotal
Mean30.0 ± 7.1631.8 ± 9.9530.9 ± 8.63
Body Mass Index
Body Mass Index(kilograms per square meter)Placebo150 mg Ivacaftor q12hTotal
Mean16.8 ± 1.7517.1 ± 2.6117.0 ± 2.21

3 further baseline measures are reported on the registry.

08

Study locations

29 sites
  • University of Alabama
    Birmingham, Alabama 35233-1711, United States
  • Emory Cystic Fibrosis Center
    Atlanta, Georgia 30322, United States
  • Children's Memorial Hospital
    Chicago, Illinois 60614, United States
  • The Cystic Fibrosis Center of Chicago
    Glenview, Illinois 60025, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • University of Iowa Department of Pediatrics
    Iowa City, Iowa 52242, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Children's Hospital Boston
    Boston, Massachusetts 02115, United States
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Children's Hospital of Michigan
    Detroit, Michigan 48201, United States
  • Helen DeVos Children's Hospital Spectrum Health Hospitals
    Grand Rapids, Michigan 49503, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • The Children's Mercy Hospital
    Kansas City, Missouri 64108, United States
  • University of Nebraska Medical Center Pediatric Pulmonary/ CF
    Omaha, Nebraska 68195-5190, United States
  • East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care
    Knoxville, Tennessee 37916, United States
  • University of Utah Pediatric Pulmonology
    Salt Lake City, Utah 84108, United States
  • University of Virginia Pediatric Respiratory Medicine
    Charlottesville, Virginia 22908, United States
  • The Children's Hospital Westmead
    Westmead, New South Wales 2145, Australia
  • Royal Children's Hospital Brisbane
    Herston, Queensland 4029, Australia
  • Royal Children's Hospital Melbourne
    Parkville, Victoria 3052, Australia
  • Princess Margaret Hospital for Children
    Subiaco, Western Australia 6008, Australia
  • British Columbia Children's Hospital
    Vancouver, British Columbia V6H-3V4, Canada
  • Hospital for Sick Children CF Center
    Toronto, Ontario M5G 1X8, Canada
  • Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition
    Paris, 75935, France
  • Kinder- und Jugendklinik Universitätsklinikum Erlangen
    Erlangen, 91054, Germany
  • Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
    Jena, 07740, Germany
  • Our Lady's Children's Hospital
    Dublin, 12, Ireland
  • The National Children's Hospital
    Dublin, 24, Ireland
  • Dept of Gene Therapy, Imperial College London
    London, SW3 6LR, United Kingdom
09

References and documents

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 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 21, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00909727
Lead sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation
Responsible party
Sponsor
First posted
May 28, 2009
Start date
Aug 2009
Primary completion
Nov 2010
Completion
Apr 2011
Results posted
Aug 21, 2012
Last update
Aug 21, 2012

Study contacts

Richard Ahrens, MD
principal investigator · Roy A. & Lucille A. Carver College of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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