Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2024-09-13 Epub Date: 2024-06-24 DOI:10.1016/j.medj.2024.05.018

Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Di An, Kathie M Bishop, James M Youakim

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引用次数: 0

Abstract

Background: Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER.

Methods: Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40.

Findings: Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively.

Conclusions: Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER.

Funding: The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). This trial was registered at ClinicalTrials.gov (NCT04279314).

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曲非奈德治疗雷特综合征：开放标签扩展 LILAC 研究的结果。

研究背景根据为期 12 周的 LAVENDER 3 期随机安慰剂对照研究结果，特罗非肽被批准用于治疗雷特综合征。雷特综合征是一种需要长期治疗的慢性疾病。我们报告了LILAC的疗效和安全性结果，这是一项为期40周的开放标签LAVENDER扩展研究：方法：5-21 岁患有雷特综合征的女性接受了为期 40 周的特罗菲肽开放标签治疗。主要终点是特罗非肽的长期安全性；次要终点包括第40周时雷特综合征行为问卷评分和第40周时临床总体印象-改善评分与基线相比的变化：LILAC共有154名患者接受了特罗菲肽治疗。LILAC中最常见的不良反应是腹泻（74.7%）、呕吐（28.6%）和COVID-19（11.0%）。腹泻是导致停药的最常见不良反应（21.4%）。从LAVENDER基线到LILAC第40周，接受特罗芬肽治疗和安慰剂治疗的患者的Rett综合征行为问卷平均得分（标准误差）分别为-7.3（1.62）和-7.0（1.61）。在第40周时，与LILAC基线相比，接受特罗芬肽治疗的患者和接受LAVENDER安慰剂治疗的患者的平均临床总体印象改善评分（标准误差）分别为3.1（0.11）和3.2（0.14）：结论：特罗菲肽治疗≤40周可持续改善Rett综合征的症状。特罗芬肽在LILAC中的安全性与在LAVENDER中相似：本研究得到了阿卡迪亚制药公司（Acadia Pharmaceuticals Inc.）该试验已在ClinicalTrials.gov（NCT04279314）上注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.