Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One F508del Allele: A Phase 3 Open-Label Extension Study.

Objectives: Given the potential for lifelong ELX/TEZ/IVA use, the long-term safety and efficacy of ELX/TEZ/IVA was assessed.

目标：鉴于ELX/TEZ/IVA可能需要终身使用，评估了ELX/TEZ/IVA的长期安全性和疗效。

Methods: In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function genotypes (from 24-wk parent study 445-102 [n = 399]) or with the F508del-F508del genotype (from 4-wk parent study 445-103 [n = 107]) received ELX/TEZ/IVA (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h) over 192 weeks.

方法：在这项III期、开放标签、单臂扩展研究中，F508del-最小功能基因型的参与者（来自24周的父研究445-102 [n = 399]）或F508del-F508del基因型的参与者（来自4周的父研究445-103 [n = 107]）接受了ELX/TEZ/IVA（ELX 200 mg每日一次，TEZ 100 mg每日一次，IVA 150 mg每12小时一次）治疗，持续192周。

Measurements and Main Results: The primary endpoint was safety and tolerability.

测量和主要结果：主要终点是安全性和耐受性。

Mean exposure to ELX/TEZ/IVA was 172.6 weeks.

患者对ELX/TEZ/IVA的平均暴露时间为172.6周。

Most participants had adverse events classified as mild (12.8%) or moderate (60.7%) in severity.

大多数参与者出现的不良事件被分类为轻度（12.8%）或中度（60.7%）严重程度。

Eighteen participants (3.6%) had adverse events that led to treatment discontinuation.

有18名参与者（占3.6%）因不良事件导致治疗中断。

After starting ELX/TEZ/IVA, participants had consistent increases in percent predicted FEV1 (ppFEV1), Cystic Fibrosis Questionnaire-Revised respiratory domain score, and body mass index, with decreases in sweat chloride concentration and pulmonary exacerbation rates; these improvements were maintained through 192 weeks.

在开始使用ELX/TEZ/IVA后，参与者的预计用力肺活量百分比（ppFEV1）、囊性纤维化问卷修订版呼吸领域评分和体重指数持续增加，汗液氯化物浓度和肺部急性加重率下降；这些改善持续至192周。

The mean annualized rate of change in ppFEV1 was 0.02 percentage points (95% confidence interval, -0.14 to 0.19) after initiation of ELX/TEZ/IVA.

在开始使用ELX/TEZ/IVA后，ppFEV1的平均年化变化率为0.02个百分点（95%置信区间，-0.14至0.19）。

Conclusions: During this 192-week open-label extension study, the longest clinical study of a CFTR (cystic fibrosis transmembrane conductance regulator) modulator to date, ELX/TEZ/IVA remained generally safe and well tolerated.

结论：在这项为期192周的开放标签扩展研究中，这是迄今为止最长的CFTR（囊性纤维化跨膜传导调节器）调节剂的临床研究，ELX/TEZ/IVA总体上保持了安全性和良好的耐受性。

Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates, and nutritional status.

参与者在肺功能、呼吸症状、囊性纤维化跨膜调节因子（CFTR）功能、肺部急性加重率和营养状况方面持续改善。

The estimated annualized rate of change in ppFEV1 suggests no evidence of pulmonary function loss across the study population over the 4-year treatment period.

在4年的治疗期间，ppFEV1的估计年化变化率表明，研究人群中没有肺功能丧失的证据。

These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF.

这些结果确认了ELX/TEZ/IVA在青少年和成年囊性纤维化患者中具有良好的长期安全性特征和持久的疾病修饰性临床益处。

Clinical trial registered with www.clinicaltrials.gov (NCT03525574).

临床试验已注册于www.clinicaltrials.gov (NCT03525574)。