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

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00909727
First received: May 26, 2009
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: Ivacaftor
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: No ]
    Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.


Secondary Outcome Measures:
  • Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 [ Time Frame: baseline through 48 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 52
Study Start Date: August 2009
Study Completion Date: April 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
Drug: Placebo
Tablet given orally q12h for up to 48 weeks
Experimental: 150 mg Ivacaftor q12h
Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
Drug: Ivacaftor
150-mg tablet given orally q12h for up to 48 weeks
Other Name: VX-770

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.

  Eligibility

Ages Eligible for Study:   6 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909727

  Show 29 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Richard Ahrens, MD Roy A. & Lucille A. Carver College of Medicine
  More Information

Additional Information:
No publications provided by Vertex Pharmaceuticals Incorporated

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00909727     History of Changes
Other Study ID Numbers: VX08-770-103
Study First Received: May 26, 2009
Results First Received: February 27, 2012
Last Updated: July 18, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medicines Board
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada

Keywords provided by Vertex Pharmaceuticals Incorporated:
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 23, 2014