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

Cystic Fibrosis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909727
• Other study ID #: VX08-770-103
• Status: Completed
• Phase: Phase 3
• First received: May 26, 2009
• Last updated: July 18, 2012
• Start date: August 2009
• Est. completion date: April 2011

Study information

• Verified date: July 2012
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIreland: Irish Medicines BoardFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 11 Years

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Ivacaftor
150-mg tablet given orally q12h for up to 48 weeks
• Placebo
Tablet given orally q12h for up to 48 weeks

Locations

Country	Name	City	State
Australia	Royal Children's Hospital Brisbane	Herston	Queensland
Australia	Royal Children's Hospital Melbourne	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Subiaco	Western Australia
Australia	The Children's Hospital Westmead	Westmead	New South Wales
Canada	Hospital for Sick Children CF Center	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
France	Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition	Paris
Germany	Kinder- und Jugendklinik Universitätsklinikum Erlangen	Erlangen
Germany	Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin	Jena
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	The National Children's Hospital	Dublin
United Kingdom	Dept of Gene Therapy, Imperial College London	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Cystic Fibrosis Center	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Pediatric Respiratory Medicine	Charlottesville	Virginia
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	The Cystic Fibrosis Center of Chicago	Glenview	Illinois
United States	Helen DeVos Children's Hospital Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa Department of Pediatrics	Iowa City	Iowa
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care	Knoxville	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Nebraska Medical Center Pediatric Pulmonary/ CF	Omaha	Nebraska
United States	University of Utah Pediatric Pulmonology	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	Cystic Fibrosis Foundation Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline through 24 weeks	No
Secondary	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.	baseline through 48 weeks	No
Secondary	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).	baseline through 24 weeks and 48 weeks	No
Secondary	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.	baseline through 24 weeks and 48 weeks	No
Secondary	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.	baseline to 24 weeks and 48 weeks	No

External Links

•   Genetics Home Reference
•   Medline Plus
•   U.S. FDA Resources