Background

The CFTR modulator tezacaftor/ivacaftor was efficacious and generally safe and well tolerated in Phase 3 studies in participants ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous with a residual function-CFTR mutation (F/F or F/RF respectively). We evaluated tezacaftor/ivacaftor's efficacy and safety over 8 weeks in participants 6 through 11 years of age with these mutations.

Methods

Participants were randomized 4:1 to tezacaftor/ivacaftor or a blinding group (placebo for F/F, ivacaftor for F/RF). The primary endpoint was within-group change from baseline in the lung clearance index 2·5 (LCI_2·5) through Week 8. Secondary endpoints were change from baseline in sweat chloride (SwCl), cystic fibrosis questionnaire-revised (CFQ-R) respiratory domain score, and safety.

Results

Sixty-seven participants received at least one study drug dose. Of those, 54 received tezacaftor/ivacaftor (F/F, 42; F/RF, 12), 10 placebo, and 3 ivacaftor; 66 completed the study. The within-group change in LCI_2·5 was significantly reduced (improved) by −0·51 (95% CI: −0·74, −0·29). SwCl concentration decreased (improved) by −12·3 mmol/L and CFQ-R respiratory domain score increased (improved, nonsignificantly) by 2·3 points. There were no serious adverse events (AEs) or AEs leading to tezacaftor/ivacaftor discontinuation or interruption. The most common AEs (≥10%) in participants receiving tezacaftor/ivacaftor were cough, headache, and productive cough.

Conclusions

Tezacaftor/ivacaftor improved lung function (assessed using LCI) and CFTR function (measured by SwCl concentration) in participants 6 through 11 years of age with F/F or F/RF genotypes. Tezacaftor/ivacaftor was safe and well tolerated; no new safety concerns were identified.

中文翻译：

---

一项 3 期、双盲、平行组研究，旨在评估 tezacaftor 与依伐卡托联用在 6 至 11 岁患有囊性纤维化 F508del 纯合子或 F508del-CFTR 突变杂合子和残留功能的参与者中的疗效和安全性突变

背景

该CFTR调节tezacaftor / ivacaftor是有效和普遍安全和相位良好的耐受性3项研究中参与者≥12年的纯合子年龄囊性纤维化（CF）F508del-CFTR突变或杂有残留的功能- CFTR突变（F / F或F /RF ）。我们在 8 周内评估了 tezacaftor/ivacaftor 在具有这些突变的 6 至 11 岁参与者中的疗效和安全性。

方法

参与者按 4:1 随机分配至 tezacaftor/ivacaftor 或盲法组（F/F安慰剂，F /RF ivacaftor ）。主要终点是肺清除指数 2·5 (LCI _2·5 ) 从基线到第 8 周的组内变化。次要终点是汗液氯化物 (SwCl) 从基线的变化，囊性纤维化问卷修订版 (CFQ-R) ) 呼吸领域评分和安全性。

结果

67 名参与者至少接受了一种研究药物剂量。其中，54 人接受了 tezacaftor/ivacaftor（F/F，42；F /RF，12）、10 人安慰剂和 3 人 ivacaftor；66人完成了研究。LCI _2·5的组内变化显着降低（改善）-0·51（95% CI：-0·74，-0·29）。SwCl 浓度降低（改善）-12·3 mmol/L，CFQ-R 呼吸域评分增加（改善，不显着）2·3 分。没有导致 tezacaftor/ivacaftor 停药或中断的严重不良事件 (AE) 或 AE。接受 tezacaftor/ivacaftor 的参与者中最常见的 AE (≥10%) 是咳嗽、头痛和咳痰。

结论

Tezacaftor/ivacaftor 改善了 6 至 11 岁F/F或F /RF 基因型参与者的肺功能（使用 LCI 评估）和 CFTR 功能（通过 SwCl 浓度测量）。Tezacaftor/ivacaftor 安全且耐受性良好；没有发现新的安全问题。