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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivacaftor
Placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Pathologic Processes

Eligibility Criteria

6 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Alabama
  • Emory Cystic Fibrosis Center
  • Children's Memorial Hospital
  • The Cystic Fibrosis Center of Chicago
  • Riley Hospital for Children
  • University of Iowa Department of Pediatrics
  • Massachusetts General Hospital
  • Children's Hospital Boston
  • University of Michigan
  • Children's Hospital of Michigan
  • Helen DeVos Children's Hospital Spectrum Health Hospitals
  • University of Minnesota
  • The Children's Mercy Hospital
  • University of Nebraska Medical Center Pediatric Pulmonary/ CF
  • East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care
  • University of Utah Pediatric Pulmonology
  • University of Virginia Pediatric Respiratory Medicine
  • The Children's Hospital Westmead
  • Royal Children's Hospital Brisbane
  • Royal Children's Hospital Melbourne
  • Princess Margaret Hospital for Children
  • British Columbia Children's Hospital
  • Hospital for Sick Children CF Center
  • Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition
  • Kinder- und Jugendklinik Universitätsklinikum Erlangen
  • Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
  • Our Lady's Children's Hospital
  • The National Children's Hospital
  • Dept of Gene Therapy, Imperial College London

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

150 mg Ivacaftor q12h

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.

Full Information

First Posted
May 26, 2009
Last Updated
July 18, 2012
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00909727
Brief Title
Study of Ivacaftor in Cystic Fibrosis Subjects Aged 6 to 11 Years With the G551D Mutation
Acronym
ENVISION
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Fibrosis, Pancreatic Diseases, Digestive System Diseases, Lung Diseases, Respiratory Tract Diseases, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Pathologic Processes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
Arm Title
150 mg Ivacaftor q12h
Arm Type
Experimental
Arm Description
Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
VX-770
Intervention Description
150-mg tablet given orally q12h for up to 48 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet given orally q12h for up to 48 weeks
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Description
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 Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48
Description
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
Title
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)
Description
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
Title
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48
Description
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
Title
Absolute Change From Baseline in Weight at Week 24 and Week 48
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Ahrens, MD
Organizational Affiliation
Roy A. & Lucille A. Carver College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233-1711
Country
United States
Facility Name
Emory Cystic Fibrosis Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
The Cystic Fibrosis Center of Chicago
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60025
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Department of Pediatrics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Helen DeVos Children's Hospital Spectrum Health Hospitals
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
The Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
University of Nebraska Medical Center Pediatric Pulmonary/ CF
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68195-5190
Country
United States
Facility Name
East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37916
Country
United States
Facility Name
University of Utah Pediatric Pulmonology
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Virginia Pediatric Respiratory Medicine
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
The Children's Hospital Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Children's Hospital Brisbane
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Royal Children's Hospital Melbourne
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Princess Margaret Hospital for Children
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
British Columbia Children's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H-3V4
Country
Canada
Facility Name
Hospital for Sick Children CF Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition
City
Paris
ZIP/Postal Code
75935
Country
France
Facility Name
Kinder- und Jugendklinik Universitätsklinikum Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Our Lady's Children's Hospital
City
Dublin
ZIP/Postal Code
12
Country
Ireland
Facility Name
The National Children's Hospital
City
Dublin
ZIP/Postal Code
24
Country
Ireland
Facility Name
Dept of Gene Therapy, Imperial College London
City
London
ZIP/Postal Code
SW3 6LR
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23590265
Citation
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.
Results Reference
derived
Links:
URL
http://ghr.nlm.nih.gov/
Description
Genetics Home Reference
URL
http://www.nlm.nih.gov/medlineplus/
Description
Medline Plus
URL
http://www.clinicaltrials.gov/ct2/info/fdalinks
Description
U.S. FDA Resources

Learn more about this trial

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

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