Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation

Cystic Fibrosis Clinical Trial

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Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00953706
• Other study ID #: VX08-770-104
• Secondary ID: 2009-010261-23
• Status: Terminated
• Phase: Phase 2
• First received: August 4, 2009
• Last updated: August 27, 2015
• Start date: September 2009
• Est. completion date: May 2013

Study information

• Verified date: August 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Ivacaftor is a potent and selective CFTR 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 study investigated the effects of ivacaftor in participants with cystic fibrosis (CF) >=12 years of age with a forced expiratory volume in 1 second (FEV1) >=40 percent (%) predicted. This study was conducted in 2 parts.

• Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of participants with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation.

• Part B of this study was an open-label extension of Part A, enrolling participants who completed Part A and met pre-specified endpoint criteria, and explored the safety and efficacy of ivacaftor over long-term treatment in participants with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 140
• Est. completion date: May 2013
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation

• Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height

• Willing to use at least 2 highly effective birth control methods during the study

• No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator

• Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, 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

• History of alcohol, medication or illicit drug abuse within one year prior to Day 1

• Abnormal liver function >=3 x the upper limit of normal

• Abnormal renal function at Screening

• History of solid organ or hematological transplantation

• Pregnant or breast-feeding (for women)

• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening

• Previous participation in a VX-809 study

• Used inhaled hypertonic saline treatment

• Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)

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
Tablet
• Placebo
Tablet

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	Providence Medical Center	Anchorage	Alaska
United States	University of Alabama	Birmingham	Alabama
United States	St. Luke's CF clinic	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Vermont Lung Center at the University of Vermont	Colchester	Vermont
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital; Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	New York Medical College	Hawthorne	New York
United States	Hershey Medical Center	Hershey	Pennsylvania
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	The CF Center, Beth Israel Medical Center	New York City	New York
United States	Kaiser Permanente Medical Care Program	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nemours Children's Clinic	Orlando	Florida
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Medical College of Virginia	Richmond	Virginia
United States	Univeristy of Utah	Salt Lake City	Utah
United States	Toldedo Children's Hospital	Toledo	Ohio
United States	University of Massachussetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	Cystic Fibrosis Foundation Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16	Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.	Part A baseline through Week 16	No
Secondary	Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16	The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.	Part A baseline through Week 16	No
Secondary	Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16	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.	Part A baseline through Week 16	No
Secondary	Part A : Rate of Change From Baseline in Weight Through Week 16	As malnutrition is common in participants 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.	Part A baseline through Week 16	No
Secondary	Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64	ppFEV1 is defined in Outcome Measure 1.	Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64	No
Secondary	Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64	ppFEV1 is defined in Outcome Measure 1.	Part A baseline through Week 64	No
Secondary	Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64	ppFEV1 is defined in Outcome Measure 1.	Part B baseline through Week 64	No
Secondary	Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64	The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.	Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64	No
Secondary	Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64	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.	Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64	No
Secondary	Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64	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 Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64	No
Secondary	Part B : Number of Participants With Pulmonary Exacerbations	Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.	Part B baseline through Week 64	No
Secondary	Part B : Number of Pulmonary Exacerbation Events	Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.	Part B baseline through Week 64	No
Secondary	Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year	Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.	Part B baseline through Week 64	No

External Links

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