A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive CFTR Mutation and No F508del Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 597
- 试验地点
- 170
- 主要终点
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no F508del 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
- 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
- •Participant has one of the following genotypes:
- •Homozygous for F508del;
- •Heterozygous for F508del and a gating (F/G) mutation;
- •Heterozygous for F508del and a residual function (F/RF) mutation;
- •At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA and no F508del mutation
- •Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving CFTR protein modulator therapy; FEV1 >=40% and <=80% for participants not currently receiving CFTR protein modulator therapy
排除标准
- •History of solid organ or hematological transplantation
- •Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Pregnant or breast-feeding females
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
VX-121/TEZ/D-IVA
Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
干预措施: Placebo (matched to IVA) (Drug)
ELX/TEZ/IVA
Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
干预措施: ELX/TEZ/IVA (Drug)
ELX/TEZ/IVA
Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
干预措施: IVA (Drug)
ELX/TEZ/IVA
Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
干预措施: Placebo (matched to VX-121/TEZ/D-IVA) (Drug)
VX-121/TEZ/D-IVA
Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
干预措施: VX-121/TEZ/D-IVA (Drug)
VX-121/TEZ/D-IVA
Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
干预措施: Placebo (matched to ELX/TEZ/IVA) (Drug)
结局指标
主要结局
Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)
时间窗: From Baseline 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 in Sweat Chloride (SwCl)(From Baseline Through Week 24)
- Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)(From Baseline Through Week 24)
- Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)(From Baseline Through Week 24)