A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 405
- 试验地点
- 115
- 主要终点
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
研究概览
简要总结
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heterozygous for the F508del mutation (F/MF)
- •Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
排除标准
- •Clinically significant cirrhosis with or without portal hypertension
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Solid organ or hematological transplantation
- •Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Placebo
Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
干预措施: Placebo (Drug)
VX-445/TEZ/IVA TC
Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
干预措施: VX-445/TEZ/IVA (Drug)
VX-445/TEZ/IVA TC
Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
干预措施: IVA (Drug)
结局指标
主要结局
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
时间窗: From Baseline at Week 4
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)(From Baseline through Week 24)
- Number of Pulmonary Exacerbations (PEx)(From Baseline through Week 24)
- Time-to-first Pulmonary Exacerbation (PEx)(From Baseline through Week 24)
- Absolute Change in Body Weight(From Baseline at Week 24)
- Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score(From Baseline at Week 4)
- Absolute Change in Sweat Chloride(From Baseline at Week 4)
- Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline(From Baseline at Week 24)
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline through Week 24)
- Absolute Change in Body Mass Index (BMI)(From Baseline at Week 24)
- Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks))
- Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA(Pre-dose on Week 4, 8, 12, and 16)