Clinical trial NCT00953706: Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2009-08-06
Enrollment: 140
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
timeFrame: Part A baseline through Week 16
Secondary outcomes:
measure: Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
timeFrame: Part A baseline through Week 16
measure: Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
timeFrame: Part A baseline through Week 16
measure: Part A : Rate of Change From Baseline in Weight Through Week 16
timeFrame: Part A baseline through Week 16
measure: Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
timeFrame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
measure: Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64
timeFrame: Part A baseline through Week 64
measure: Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64
timeFrame: Part B baseline through Week 64
measure: Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64
timeFrame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
measure: Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
timeFrame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
measure: Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64
timeFrame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64
measure: Part B : Number of Participants With Pulmonary Exacerbations
timeFrame: Part B baseline through Week 64
measure: Part B : Number of Pulmonary Exacerbation Events
timeFrame: Part B baseline through Week 64
measure: Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
timeFrame: Part B baseline through Week 64
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Anchorage
country: United States
facility: Providence Medical Center
state: Alaska
city: Oakland
country: United States
facility: Kaiser Permanente Medical Care Program
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Boise
country: United States
facility: St. Luke's CF clinic
state: Idaho
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachussetts Medical School
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital; Spectrum Health Hospitals
state: Michigan
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: Hawthorne
country: United States
facility: New York Medical College
state: New York
city: New York City
country: United States
facility: The CF Center, Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Toldedo Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Univeristy of Utah
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center at the University of Vermont
state: Vermont
city: Richmond
country: United States
facility: Medical College of Virginia
state: Virginia
Study officials:
affiliation: Medical University of South Carolina
name: Patrick A Flume, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordonez CL, Geller DE; VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672.