A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 70
- 主要终点
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have the R117H-CFTR mutation.
详细描述
Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical benefit in subjects with CF. Results from Phase 3 studies (VX08-770-102 [Study 102] [NCT00909532] and VX08-770-103 [Study 103] [NCT00909727]) showed that ivacaftor is effective in the treatment of subjects with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR channel function (measured by reduction in sweat chloride concentration) and corresponding substantial, durable improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature discontinuation and results of safety assessments.
Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States for the treatment of CF in subjects 6 years of age and older who have a G551D mutation in the CFTR gene.
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
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female with confirmed diagnosis of CF
- •Must have at least 1 allele of the R117H CFTR mutation
- •Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) predicted normal for age, sex, and height
- •6 years of age or older
- •Minimum weight of 15 kilogram (kg) at screening
- •Females of childbearing potential must not be pregnant
- •Willing to comply with contraception requirements
排除标准
- •CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D)
- •History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
- •Abnormal liver function, at screening, defined as greater than or equal to (>=) 3 time upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), total bilirubin
- •Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening
- •History of solid organ or hematological transplantation
- •History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
- •Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
- •Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis)
- •Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
研究组 & 干预措施
Ivacaftor
Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.
干预措施: Ivacaftor (Drug)
Placebo
Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
时间窗: Baseline, Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years.
次要结局
- Change From Baseline in Body Mass Index (BMI) at Week 24(Baseline, Week 24)
- Change From Baseline in Sweat Chloride Through Week 24(Baseline, Week 24)
- Time to First Pulmonary Exacerbation(Day 0 to 15, Day 16 to 56, Day 57 to 112, Day 113 to 168)
- Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24(Baseline, Week 24)
- Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24]))