A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 39
- 主要终点
- Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
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 a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).
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
- Crossover
- 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
- •At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D
- •Percent predicted forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) 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
- •G551D-CFTR mutation on at least 1 allele
- •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
- •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
- •Use of inhaled hypertonic saline treatment
- •Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
- •Evidence of cataract or lens opacity at screening
研究组 & 干预措施
Part 1: Ivacaftor First, Then Placebo
Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
干预措施: Ivacaftor (Drug)
Part 1: Ivacaftor First, Then Placebo
Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
干预措施: Placebo (Drug)
Part 1: Placebo First, Then Ivacaftor
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
干预措施: Ivacaftor (Drug)
Part 1: Placebo First, Then Ivacaftor
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
干预措施: Placebo (Drug)
Part 2: Ivacaftor
Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
时间窗: Part 1: Baseline (pre-dose Day 1), Week 8
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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit)
时间窗: Baseline (pre-dose Week 12), Week 36
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. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
次要结局
- Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8(Part 1: Baseline (pre-dose Day 1), Week 8)
- Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit)(Baseline (pre-dose Week 12), Week 36)
- Part 1: Change From Baseline in Sweat Chloride Through Week 8(Part 1: Baseline (pre-dose Day 1), Week 8)
- Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit)(Baseline (pre-dose Week 12), Week 36)
- Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8(Part 1: Baseline (pre-dose Day 1), Week 8)
- Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit)(Baseline (pre-dose Week 12), Week 36)
- Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Part 1: From signing of informed consent up to Week 20)
- Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Part 2: Week 20 up to Week 40)