Wainwright Claire, McColley Susanna A, McNally Paul, Powers Michael, Ratjen Felix A, Rayment Jonathan H, Retsch-Bogart George, Roesch Erica, Ramsey Bonnie, McKone Edward F, Tullis Elizabeth, Mall Marcus A, Taylor-Cousar Jennifer L, Waltz David, Ahluwalia Neil, Chu Chenghao, Scirica Christina V, Davies Jane C
Royal Children's Hospital, Respiratory Medicine, Brisbane, Queensland, Australia;
Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States.
Am J Respir Crit Care Med. 2025 Jun 2. doi: 10.1164/rccm.202502-0512OC.
Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children 6 through 11 years of age with cystic fibrosis (CF) and at least one allele in a 24-week phase 3 study. Children completing this study could enroll into a 192-week extension study.
Evaluate long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years.
In this 2-part (Part A [96-weeks] and Part B [96-weeks]) phase 3 extension study, children <12 years weighing <30 kg received ELX 100 mg once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and children weighing ≥ 30 kg or aged ≥12 years received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h.
Sixty-four children (/MF [n=36] and [n=28]) received ≥ 1 dose of ELX/TEZ/IVA. Mean exposure was 156.2 weeks and 60.9% of children (n=39) completed treatment in both parts of this 192-week study. The primary endpoint was safety. All children had adverse events (AEs), which for most were mild (31.3%) or moderate (64.1%) and generally consistent with common manifestations of CF. Two children (3.1%) had non-serious AEs that lead to treatment discontinuation (increased alanine aminotransferase [n=1] and aggression [n=1]). Secondary endpoints focused on efficacy. From parent study baseline, improvements were seen in ppFEV (9.6 percentage points; 95% CI: 5.4, 13.7), sweat chloride concentration (-57.9 mmol/L; 95% CI: -63.3, -52.5), CFQ-R respiratory domain score (10.0 points; 95% CI: 6.9, 13.0), LCI (-2.33; 95% CI: -2.87, -1.79), and BMI z-score (0.39; 95% CI: 0.19, 0.59) at Week 192. Rate of pulmonary exacerbations per year was 0.05. The annualized rate of change in ppFEV and LCI was -0.09 percentage points (95% CI: -1.01, 0.84) and -0.07 units (95%CI: -0.12, -0.01), respectively.
In this 4-year extension study in children ≥6 years, the longest clinical trial experience with a CFTR modulator in this pediatric population, ELX/TEZ/IVA remained generally safe and well-tolerated with no new safety findings. Clinically meaningful improvements in lung function, CFTR function, and nutritional status reported in the parent study were maintained. These results confirm the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.
gov, ID: NCT04183790.
在一项为期24周的3期研究中，埃莱沙卡福/特扎卡福/依伐卡福（ELX/TEZ/IVA）被证明对6至11岁患有囊性纤维化（CF）且至少有一个等位基因的儿童是安全有效的。完成该研究的儿童可以参加一项为期192周的扩展研究。
评估ELX/TEZ/IVA在≥6岁儿童中的长期安全性和有效性。
在这项分为两部分（A部分[96周]和B部分[96周]）的3期扩展研究中，体重<30 kg的<12岁儿童接受ELX 100 mg每日一次（qd）/TEZ 50 mg qd/IVA 75 mg每12小时一次（q12h），体重≥30 kg或年龄≥12岁的儿童接受ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h。
64名儿童（男/女[n = 36]和[n = 28]）接受了≥1剂ELX/TEZ/IVA。平均暴露时间为156.2周，在这项为期192周的研究的两个部分中，60.9%的儿童（n = 39）完成了治疗。主要终点是安全性。所有儿童都有不良事件（AE），大多数为轻度（31.3%）或中度（64.1%），通常与CF的常见表现一致。两名儿童（3.1%）发生了导致治疗中断的非严重AE（丙氨酸转氨酶升高[n = 1]和攻击行为[n = 1]）。次要终点集中在疗效上。从母研究基线来看，在第192周时，ppFEV（9.6个百分点；95%CI：5.4，13.7）、汗液氯化物浓度（-57.9 mmol/L；95%CI：-63.3，-52.5）、CFQ-R呼吸领域评分（10.0分；95%CI：6.9，13.0）、LCI（-2.33；95%CI：-2.87，-1.79）和BMI z评分（0.39；95%CI：0.19，0.59）均有改善。每年肺部加重的发生率为0.05。ppFEV和LCI的年化变化率分别为-0.09个百分点（95%CI：-1.01，0.84）和-0.07单位（95%CI：-0.12，-0.01）。
在这项针对≥6岁儿童的为期4年的扩展研究中，这是该儿科人群中使用CFTR调节剂的最长临床试验经验，ELX/TEZ/IVA总体上仍然安全且耐受性良好，没有新的安全性发现。母研究中报告的肺功能、CFTR功能和营养状况的临床有意义的改善得以维持。这些结果证实了ELX/TEZ/IVA在≥6岁儿童中的长期安全性和有效性。本文是开放获取的，并根据知识共享署名非商业性无衍生作品许可协议4.0（http://creativecommons.org/licenses/by-nc-nd/4.0/）分发。临床试验注册可在www.CLINICALTRIALS.gov上查询，ID：NCT04183790。
