A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 563
- 主要终点
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
研究概览
简要总结
The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.
详细描述
This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter study of orally administered lumacaftor in combination with ivacaftor in participants aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.
The study included a Screening Period (Day -28 through Day -1), a Treatment Period (Day 1 [first dose of study drug] to Week 24 ± 5 days), and a Safety Follow-up Visit (4 weeks ± 7 days after the Week 24 Visit).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of CF
- •Homozygous for the F508del CFTR mutation
- •Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) and less than or equal to (=<) 90% of predicted normal for age, sex, and height
- •Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
排除标准
- •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
- •History of solid organ or hematological transplantation
- •History of alcohol or drug abuse in the past year
- •Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
- •Use of strong inhibitors, moderate inducers, or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing
研究组 & 干预措施
Placebo
Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24.
干预措施: Placebo (Drug)
LUM 600 mg qd/IVA 250 mg q12h
LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
干预措施: Lumacaftor Plus Ivacaftor Combination (Drug)
LUM 600 mg qd/IVA 250 mg q12h
LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
干预措施: Ivacaftor (Drug)
LUM 400 mg q12h/ IVA 250 mg q12h
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
干预措施: Lumacaftor Plus Ivacaftor Combination (Drug)
结局指标
主要结局
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
时间窗: Baseline, Week 16 and 24
Absolute change from baseline at week 24 was assessed as the average treatment effect at Week 16 and at Week 24. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
次要结局
- Absolute Change From Baseline in Body Mass Index (BMI) at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Scores at Week 24(Baseline, Week 24)
- Pre-dose Concentration (Ctrough), Average Pre-dose Concentration (Ctrough,Avg), 3 to 6 Hours Post-dose Concentration (C3-6h), and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Avg)(For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16)
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in BMI-for-age Z-score at Week 24(Baseline, Week 24)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)(up to Week 28)
- Number of Pulmonary Exacerbation Events(through Week 24)
- Percentage of Participants With At Least 1 Pulmonary Exacerbation Event(through Week 24)
- Relative Change From Baseline in Percent Predicted FEV1 at Week 24(Baseline, Week 16 and 24)
- Percentage of Participants With Response Based on Percent Predicted FEV1(Week 16 and 24)
- Absolute Change From Baseline in Weight at Week 24(Baseline, Week 24)
- Time-to-First Pulmonary Exacerbation(through Week 24)
- Absolute Change From Baseline in EQ-5D-3L VAS Score at Week 24(Baseline, Week 24)
- Absolute Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Index Score at Week 24(Baseline, Week 24)