An Exploratory Phase 2, 2-part, Randomized, Double-blind, Placebo-controlled Study With a Long-term, Open-label Period to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 5
- 主要终点
- Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
研究概览
简要总结
This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).
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)
盲法说明
Double blinded in Part 1, and Open label in Part 2
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with confirmed diagnosis of CF.
- •Homozygous for F508del (F/F).
- •Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.
排除标准
- •Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
- •Solid organ or hematological transplantation.
- •History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 1: Placebo
Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks.
干预措施: Placebo (Drug)
Part 1: LUM/IVA
Participants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks.
干预措施: LUM/IVA (Drug)
Part 2: Overall LUM/IVA
Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks.
干预措施: LUM/IVA (Drug)
结局指标
主要结局
Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
时间窗: From Baseline at Week 48
MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = \<50% of lobe involved and 2 = \>=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.
次要结局
- Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48(From Baseline Through Week 48)
- Part 1: Absolute Change in Weight-for-age Z-score at Week 48(From Baseline at Week 48)
- Part 1: Absolute Change in Stature-for-age Z-score at Week 48(From Baseline at Week 48)
- Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48(From Baseline at Week 48)