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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 140
- 试验地点
- 34
- 主要终点
- Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Placebo
Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
干预措施: Ivacaftor (Drug)
Placebo
Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
干预措施: Placebo (Drug)
Ivacaftor
Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
时间窗: Part A baseline 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.
次要结局
- Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16(Part A baseline through Week 16)
- Part A : Rate of Change From Baseline in Weight Through Week 16(Part A baseline through Week 16)
- Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64(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(Part A baseline through Week 64)
- Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16(Part A baseline through Week 16)
- Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64(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(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(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(Part B baseline through Week 64)
- Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64(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 Pulmonary Exacerbation Events(Part B baseline through Week 64)
- Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year(Part B baseline through Week 64)