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

Phase 2TerminatedNCT00953706

Vertex Pharmaceuticals Incorporated140 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

140

Conditions

Cystic Fibrosis

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: Part A baseline through Week 16

Secondary Outcomes

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.

Time frame: Part A baseline through Week 16

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.

Time frame: Part A baseline through Week 16

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.

Time frame: Part A baseline through Week 16

Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64

ppFEV1 is defined in Outcome Measure 1.

Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64

ppFEV1 is defined in Outcome Measure 1.

Time frame: Part A baseline through Week 64

Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64

ppFEV1 is defined in Outcome Measure 1.

Time frame: Part B baseline through Week 64

Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64

Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64

Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

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.

Time frame: Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

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.

Time frame: Part B baseline through Week 64

Part B : Number of Pulmonary Exacerbation Events

Time frame: Part B baseline through Week 64

Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year

Time frame: Part B baseline through Week 64

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

Overview

Conditions

Interventions

Eligibility

Locations (34)

Outcomes

Primary Outcomes

Secondary Outcomes