A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 主要终点
- PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Homozygous for the F508del CFTR mutation
- •FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
- •Stable CF disease as judged by the investigator
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
- •Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
- •Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
- •The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
研究组 & 干预措施
PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h
Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.
干预措施: VX-661 (Drug)
PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h
Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.
干预措施: Ivacaftor (Drug)
PC Phase: VX 661 placebo q12h + IVA placebo q12h
Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.
干预措施: Placebo matched to VX-661 (Drug)
PC Phase: VX 661 placebo q12h + IVA placebo q12h
Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.
干预措施: Placebo matched to Ivacaftor (Drug)
PC Phase: VX-661 100 mg qd + IVA 150 mg q12h
Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.
干预措施: VX-661 (Drug)
PC Phase: VX-661 100 mg qd + IVA 150 mg q12h
Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.
干预措施: Ivacaftor (Drug)
PC Phase: VX -661 placebo qd + IVA placebo q12h
Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.
干预措施: Placebo matched to VX-661 (Drug)
PC Phase: VX -661 placebo qd + IVA placebo q12h
Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.
干预措施: Placebo matched to Ivacaftor (Drug)
OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h
Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.
干预措施: VX-661 (Drug)
OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h
Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.
干预措施: Ivacaftor (Drug)
结局指标
主要结局
PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline (PC Phase) up to 112 days
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs
时间窗: Baseline (OLE Phase) up to 364 days
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
次要结局
- OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40(Baseline (OLE Phase), Through Week 40)
- PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12(Baseline (PC Phase), Through Week 12)
- PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12(Baseline (PC Phase), Week 12)
- OLE Phase: Absolute Change From Baseline BMI at Week 40(Baseline (OLE Phase), Week 40)
- PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12(Baseline (PC Phase), Through Week 12)
- OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40(Baseline (OLE Phase), Through Week 40)
- PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12(Baseline (PC Phase), Through Week 12)
- OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40(Baseline (OLE Phase), Through Week 40)
- PC Phase: Absolute Change From Baseline in Body Weight at Week 12(Baseline (PC Phase), Week 12)
- OLE Phase: Absolute Change From Baseline in Body Weight at Week 40(Baseline (OLE Phase), Week 40)
- PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12(Baseline (PC Phase), Through Week 12)
- OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40(Baseline (OLE Phase), Through Week 40)
- PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA(Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85)
- PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661(Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85)
- PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA(Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85)
- PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA(Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85)