A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 26
- 主要终点
- Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Part 1: Heterozygous for F508del and an MF mutation (F/MF)
- •Part 2: Homozygous for F508del (F/F)
- •FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height
排除标准
- •History of clinically significant cirrhosis with or without portal hypertension
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •History of solid organ or hematological transplantation
- •Other protocol-defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Part 1: Placebo
Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
干预措施: Placebo (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Low Dose
Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
干预措施: VX-121 (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Low Dose
Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
干预措施: TEZ (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Low Dose
Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
干预措施: VX-561 (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: VX-121 (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: TEZ (Drug)
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: VX-561 (Drug)
Part 1: VX-121/TEZ/VX-561 TC - High Dose
Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: VX-121 (Drug)
Part 1: VX-121/TEZ/VX-561 TC - High Dose
Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: TEZ (Drug)
Part 1: VX-121/TEZ/VX-561 TC - High Dose
Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
干预措施: VX-561 (Drug)
Part 2: TEZ/IVA
Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.
干预措施: TEZ/IVA (Drug)
Part 2: TEZ/IVA
Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.
干预措施: IVA (Drug)
Part 2: VX-121/TEZ/VX-561 TC - High Dose
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
干预措施: VX-121 (Drug)
Part 2: VX-121/TEZ/VX-561 TC - High Dose
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
干预措施: TEZ (Drug)
Part 2: VX-121/TEZ/VX-561 TC - High Dose
Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
干预措施: VX-561 (Drug)
结局指标
主要结局
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
时间窗: From Baseline Through Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
次要结局
- Absolute Change in Sweat Chloride (SwCl) Concentrations(From Baseline Through Day 29)
- Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score(From Baseline at Day 29)
- Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)(Pre-dose at Day 15 and Day 29)