Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Pediatrics, Vanderbilt Kennedy Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Med. 2024 Oct 11;5(10):1275-1281.e2. doi: 10.1016/j.medj.2024.06.007. Epub 2024 Jul 17.
Trofinetide was approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years based on the results of the 12-week, randomized, phase 3 LAVENDER study. In LILAC, a 40-week, open-label extension study of LAVENDER, trofinetide continued to improve the symptoms of RTT, with a similar safety profile as LAVENDER. Here, we report long-term safety and efficacy results of LILAC-2, a 32-month, open-label extension study.
Females aged 5-22 years who completed LILAC were eligible to enter LILAC-2. Safety and tolerability were assessed with the incidence of adverse events (AEs). Efficacy was assessed with Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scores. Caregiver interviews explored the patient's experience with RTT and the efficacy of trofinetide during study participation.
In total, 77 participants were enrolled in LILAC-2. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (standard error [SE]) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was -11.8 (2.45). The mean (SE) CGI-I score from LILAC baseline to week 12 of LILAC-2 was 3.1 (0.10). Most caregivers (96%; n = 24/25) were satisfied or very satisfied with the benefits of trofinetide.
Long-term treatment with trofinetide continued to improve RTT symptoms, without new safety concerns. Caregivers reported satisfaction with trofinetide related to improvements that were meaningful for their child and themselves.
The study was supported by Acadia Pharmaceuticals (San Diego, CA, USA). This study was registered at ClinicalTrials.gov: NCT04776746.
特立氟胺基于为期 12 周的随机、3 期 LAVENDER 研究结果，获批用于治疗年龄≥2 岁的雷特综合征（RTT）。在 LAVENDER 的 40 周、开放性扩展研究 LILAC 中，特立氟胺持续改善 RTT 症状，安全性与 LAVENDER 相似。在此，我们报告 LILAC-2 的长期安全性和疗效结果，这是一项 32 个月的开放性扩展研究。
完成 LILAC 的 5-22 岁女性有资格进入 LILAC-2。采用不良事件（AE）发生率评估安全性和耐受性。采用 Rett 综合征行为问卷（RSBQ）和临床整体印象-改善（CGI-I）评分评估疗效。通过对患者进行 caregiver访谈，了解 RTT 及特立氟胺在研究参与期间的疗效体验。
LILAC-2 共纳入 77 名参与者。最常见的 AE 是腹泻（53.2%）、COVID-19（27.3%）和呕吐（19.5%）。从 LAVENDER 基线到 LILAC-2 的第 104 周，RSBQ 评分的平均（标准误差[SE]）变化为-11.8（2.45）。从 LILAC 基线到 LILAC-2 的第 12 周，CGI-I 评分的平均（SE）为 3.1（0.10）。大多数 caregiver（96%；n=24/25）对特立氟胺的益处满意或非常满意。
特立氟胺的长期治疗持续改善 RTT 症状，无新的安全性问题。 caregiver 报告特立氟胺改善了其孩子和自己的生活，对其有益且感到满意。
本研究由 Acadia 制药公司（美国圣地亚哥）资助。该研究在 ClinicalTrials.gov 注册：NCT04776746。
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