A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 510
- 主要终点
- Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
研究概览
简要总结
This is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter study in people with cystic fibrosis (CF) who are homozygous for the F508del CF transmembrane conductance regulator (CFTR) gene mutation.
详细描述
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with Ivacaftor (IVA, VX-770). The active treatment regimen comprised of a morning dose of a fixed-dose combination (FDC) tablet of 100 milligram (mg) VX-661/150 mg IVA once daily (qd) and an evening dose of IVA 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen was visually matched tablets to be taken with the same schedule as the active treatment.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
- •Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
- •Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
- •Stable CF disease as judged by the investigator
- •Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
排除标准
- •History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
- •Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
- •Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
研究组 & 干预措施
Placebo
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
干预措施: VX-661 Plus Ivacaftor Combination Placebo (Drug)
Placebo
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
干预措施: Ivacaftor placebo (Drug)
VX-661/IVA
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
干预措施: VX-661 Plus Ivacaftor Combination (Drug)
VX-661/IVA
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
时间窗: Day 1, Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
次要结局
- Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24(Day 1, Week 24)
- Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24(Day 1, Through Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Week 28)
- Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24(Day 1, Through Week 24)
- Number of Pulmonary Exacerbations Per Year(Day 1 through Week 24)
- Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24(Day 1 through Week 24)
- Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24(Day 1, Through Week 24)
- Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)(Day 1, Week 24)
- Absolute Change From Baseline (Day 1) in Body Weight at Week 24(Day 1, Week 24)
- Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)(Pre-morning dose on Week 16)