Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for F508del and a minimal function mutation: results from a 96-week open-label extension study.

Methods

In this phase 3b extension study, dosing was based on weight and age, with children weighing <30 kg and aged <12 years receiving ELX 100 mg once daily, TEZ 50 mg once daily and IVA 75 mg every 12 h, and children ≥30 kg or ≥12 years receiving ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h.

在这项3b期扩展研究中，剂量是基于体重和年龄的，对于体重<30公斤且年龄<12岁的儿童，每天一次给予ELX 100 mg，TEZ 50 mg，每12小时一次给予IVA 75 mg；对于体重≥30公斤或≥12岁的儿童，每天一次给予ELX 200 mg，TEZ 100 mg，每12小时一次给予IVA 150 mg。

The primary end-point was safety and tolerability.

主要终点是安全性和耐受性。

Secondary and other efficacy end-points included absolute changes from parent study baseline in sweat chloride concentration, lung clearance index (LCI2.5), percentage predicted forced expiratory volume in 1 s (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.

次要和其他疗效终点包括从父研究基线开始的汗液氯化物浓度、肺清除指数（LCI2.5）、预计第一秒用力呼气量（FEV1）百分比和囊性纤维化问卷修订版（CFQ-R）呼吸领域得分的绝对变化。

Results

A total of 120 children were enrolled and dosed. 118 children (98.3%) had adverse events (AEs), which for most were mild (43.3%) or moderate (48.3%) in severity.

共有120名儿童入组并接受剂量。118名儿童（98.3%）出现不良事件（AEs），其中大多数为轻度（43.3%）或中度（48.3%）。

The most common AEs (≥20% of children) were COVID-19 (58.3%), cough (51.7%), nasopharyngitis (45.0%), pyrexia (40.0%), headache (37.5%), upper respiratory tract infection (30.8%), oropharyngeal pain (26.7%), rhinitis (24.2%), abdominal pain (22.5%) and vomiting (20.0%).

最常见的不良事件（≥20%的儿童）是COVID-19（58.3%）、咳嗽（51.7%）、鼻咽炎（45.0%）、发热（40.0%）、头痛（37.5%）、上呼吸道感染（30.8%）、口咽痛（26.7%）、鼻炎（24.2%）、腹痛（22.5%）和呕吐（20.0%）。

Children who transitioned from the placebo and ELX/TEZ/IVA groups of the parent study had improvements from parent study baseline at Week 96 in mean sweat chloride concentration (-57.3 (95% CI -61.6- -52.9) and -57.5 (95% CI -62.0- -53.0) mmol·L-1), LCI2.5 (-1.74 (95% CI -2.09- -1.38) and -2.35 (95% CI -2.72- -1.97) units), FEV1 % pred (6.1 (95% CI 2.6-9.7) and 6.9 (95% CI 3.2-10.5) percentage points) and CFQ-R respiratory domain score (6.6 (95% CI 2.5-10.8) and 2.6 (95% CI -1.6-6.8) points).

从安慰剂组和ELX/TEZ/IVA组过渡的儿童在第96周时，与父研究基线相比，平均汗液氯化物浓度有所改善（-57.3（95%置信区间-61.6至-52.9）和-57.5（95%置信区间-62.0至-53.0）mmol·L-1），LCI2.5（-1.74（95%置信区间-2.09至-1.38）和-2.35（95%置信区间-2.72至-1.97）单位），FEV1 % pred（6.1（95%置信区间2.6至9.7）和6.9（95%置信区间3.2至10.5）百分点）以及CFQ-R呼吸领域评分（6.6（95%置信区间2.5至10.8）和2.6（95%置信区间-1.6至6.8）点）。

Conclusions

ELX/TEZ/IVA treatment was generally safe and well tolerated, with a safety profile consistent with the parent study and older age groups.

ELX/TEZ/IVA治疗通常是安全且耐受性良好的，其安全性特征与父研究和老年组一致。

After starting ELX/TEZ/IVA, children had robust improvements in sweat chloride concentration and lung function that were maintained through 96 weeks.

在开始使用ELX/TEZ/IVA后，儿童的汗液氯化物浓度和肺功能显著改善，并在96周内保持稳定。

These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in this paediatric population.

这些结果展示了ELX/TEZ/IVA在这一儿童群体中的安全性和持久疗效。