Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children ≥6 Years with Cystic Fibrosis and at Least One F508del Allele: A 192-Week, Phase 3, Open-Label Extension Study.

Children completing this study could enroll into a 192-week extension study.

完成本研究的儿童可以参加一项为期192周的扩展研究。

Objectives: To evaluate the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years of age.

目的：评估ELX/TEZ/IVA在≥6岁儿童中的长期安全性和有效性。

Methods: In this two-part (part A [96 wk] and part B [96 wk]) phase 3 extension study, children <12 years of age weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, and children weighing ≥30 kg or aged ≥12 years received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours.

方法：在这项为期两部分（A部分[96周]和B部分[96周]）的3期扩展研究中，体重<30公斤且年龄<12岁的儿童每天一次接受ELX 100 mg/TEZ 50 mg/IVA 75 mg每12小时一次，而体重≥30公斤或年龄≥12岁的儿童每天一次接受ELX 200 mg/TEZ 100 mg/IVA 150 mg每12小时一次。

Measurements and Main Results: Sixty-four children (F508del/minimal function [n = 36] and F508del/F508del [n = 28]) received at least one dose of ELX/TEZ/IVA.

测量和主要结果：64名儿童（F508del/最小功能型[n=36]和F508del/F508del[n=28]）至少接受了一剂ELX/TEZ/IVA治疗。

Mean exposure was 156.2 weeks, and 60.9% of children (n = 39) completed treatment in both parts of this 192-week study.

平均暴露时间为156.2周，60.9%的儿童（n=39）完成了这项为期192周研究的两个部分的治疗。

The primary endpoint was safety.

主要终点是安全性。

All children had adverse events, which for most were mild (31.3%) or moderate (64.1%) and generally consistent with common manifestations of CF.

所有儿童均出现不良事件，其中大多数为轻度（31.3%）或中度（64.1%），且通常与囊性纤维化常见的表现一致。

Two children (3.1%) had nonserious adverse events that led to treatment discontinuation (increased alanine aminotransferase [n = 1] and aggression [n = 1]).

有两名儿童（3.1%）出现了导致治疗中断的非严重不良事件（丙氨酸氨基转移酶升高[n=1]和攻击行为[n=1]）。

Secondary endpoints focused on efficacy.

次要终点关注的是疗效。

From parent study baseline, improvements were seen in percentage predicted FEV1 (9.6 percentage points [95% confidence interval(CI), 5.4 to 13.7 percentage points]), sweat chloride concentration (-57.9 mmol/L [95% CI, -63.3 to -52.5 mmol/L]), Cystic Fibrosis Questionnaire-Revised respiratory domain score (10.0 points [95% CI, 6.9 to 13.0 points]), lung clearance index at a 2.5% stopping point (-2.33 [95% CI, -2.87 to -1.79]), and body mass index z-score (0.39 [95% CI, 0.19 to 0.59]) at Week 192.

从基线研究开始，观察到FEV1预计百分比（9.6个百分点[95%置信区间（CI），5.4至13.7个百分点]）、汗液氯化物浓度（-57.9毫摩尔/升[95% CI，-63.3至-52.5毫摩尔/升]）、囊性纤维化问卷修订版呼吸领域评分（10.0分[95% CI，6.9至13.0分]）、肺清除指数在2.5%停止点（-2.33[95% CI，-2.87至-1.79]）以及192周时体重指数z分数（0.39[95% CI，0.19至0.59]）的改善。

The rate of pulmonary exacerbations per year was 0.05.

每年的肺部急性加重发作率为0.05。

The annualized rates of change in percentage predicted FEV1 and lung clearance index at a 2.5% stopping point were -0.09 percentage points (95% CI, -1.01 to 0.84 percentage points) and -0.07 units (95% CI, -0.12 to -0.01 units), respectively.

在2.5%停止点时，预测FEV1百分比和肺清除指数的年化变化率分别为-0.09个百分点（95%置信区间，-1.01至0.84个百分点）和-0.07单位（95%置信区间，-0.12至-0.01单位）。

Conclusions: In this 4-year extension study in children ≥6 years of age, the longest clinical trial experience with a CFTR (cystic fibrosis transmembrane conductance regulator) modulator in this pediatric population, ELX/TEZ/IVA remained generally safe and well tolerated, with no new safety findings.

结论：在这项针对≥6岁儿童的为期4年的扩展研究中，作为这一儿科人群中CFTR（囊性纤维化跨膜传导调节因子）调节剂的最长临床试验经验，ELX/TEZ/IVA总体上保持安全且耐受性良好，未发现新的安全性问题。

Clinically meaningful improvements in lung function, CFTR function, and nutritional status reported in the parent study were maintained.

在主要研究中报告的肺功能、CFTR功能和营养状况的临床意义改善得到了维持。

These results confirm the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years of age.Clinical trial registered with www.clinicaltrials.gov (NCT04183790).

这些结果确认了ELX/TEZ/IVA在≥6岁儿童中的长期安全性和有效性。临床试验已在www.clinicaltrials.gov注册（NCT04183790）。