A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 21
- 主要终点
- Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
研究概览
简要总结
This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
- •Forced expiratory volume in 1 second (FEV1) value ≥40% 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
Part A: ELX/TEZ/IVA
Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.
干预措施: ELX/TEZ/IVA (Drug)
Part A: ELX/TEZ/IVA
Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.
干预措施: IVA (Drug)
Part B: ELX/TEZ/IVA
Participants in Part B weighing less than (<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
干预措施: ELX/TEZ/IVA (Drug)
Part B: ELX/TEZ/IVA
Participants in Part B weighing less than (<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
干预措施: IVA (Drug)
结局指标
主要结局
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
时间窗: Part A: Day 15
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA
时间窗: Part A: Day 15
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA
时间窗: Part A: Day 15
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
次要结局
- Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)(Part A: Day 15)
- Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs(Part A: Day 1 Through Safety Follow-up Visit (up to Day 43))
- Part B: Absolute Change in Sweat Chloride (SwCl)(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in Body Mass Index (BMI)(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Weight-for-age Z-Score(Part B: From Baseline at Week 24)
- Part B: Number of CF Related Hospitalizations(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(Part B: From Baseline Through Week 24)
- Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part B: Number of Pulmonary Exacerbations Events(Part B: From Baseline Through Week 24)
- Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)(Part B: At Week 4)
- Part B: Absolute Change in Weight(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Height(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in BMI For-Age Z-Score(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Height-for-Age Z-Score(Part B: From Baseline at Week 24)
- Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale(Part B: At Week 24)
- Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)(Part B: From Baseline Through Week 24)