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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00909727
First Posted: May 28, 2009
Last Update Posted: August 21, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
May 26, 2009
May 28, 2009
February 27, 2012
August 21, 2012
August 21, 2012
August 2009
November 2010   (Final data collection date for 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 ]
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Absolute change from baseline in percent predicted forced expiratory volume in 1 second (% predicted FEV1) through Week 24 [ Time Frame: 24 weeks ]
Complete list of historical versions of study NCT00909727 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 [ Time Frame: baseline through 48 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.
  • 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 ]
    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).
  • Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 [ Time Frame: baseline through 24 weeks and 48 weeks ]
    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.
  • Absolute Change From Baseline in Weight at Week 24 and Week 48 [ Time Frame: baseline to 24 weeks and 48 weeks ]
    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.
  • Change from baseline in sweat chloride through Week 24 and Week 48 [ Time Frame: Weeks 24 and 48 ]
  • Change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) through Week 24 and Week 48 [ Time Frame: Weeks 24 and 48 ]
  • Rate of change in weight through Week 24 and Week 48 [ Time Frame: Weeks 24 and 48 ]
  • Pharmacokinetic (PK) parameters of VX-770 [ Time Frame: 24 weeks ]
  • Absolute change from baseline in percent predicted forced expiratory volume in 1 second (% predicted FEV1) through Week 48 [ Time Frame: 48 weeks ]
Not Provided
Not Provided
 
Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: Ivacaftor
    150-mg tablet given orally q12h for up to 48 weeks
    Other Name: VX-770
  • Drug: Placebo
    Tablet given orally q12h for up to 48 weeks
  • Placebo Comparator: Placebo
    Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
    Intervention: Drug: Placebo
  • Experimental: 150 mg Ivacaftor q12h
    Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
    Intervention: Drug: Ivacaftor
Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, Mainz JG, Rodriguez S, Li H, Yen K, Ordoñez 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
April 2011
November 2010   (Final data collection date for primary outcome measure)

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:

  • 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)
Sexes Eligible for Study: All
6 Years to 11 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   France,   Germany,   Ireland,   United Kingdom,   United States
 
 
NCT00909727
VX08-770-103
Yes
Not Provided
Not Provided
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation Therapeutics
Principal Investigator: Richard Ahrens, MD Roy A. & Lucille A. Carver College of Medicine
Vertex Pharmaceuticals Incorporated
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP