齐卢可普兰治疗全身型重症肌无力患者的长期安全性和有效性：RAISE-XT开放标签扩展研究的中期分析
Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study.
作者信息
Howard James F, Bresch Saskia, Farmakidis Constantine, Freimer Miriam, Genge Angela, Hewamadduma Channa, Hinton John, Hussain Yessar, Juntas-Morales Raul, Kaminski Henry J, Maniaol Angelina, Mantegazza Renato, Masuda Masayuki, Nowak Richard J, Sivakumar Kumaraswamy, Śmiłowski Marek, Utsugisawa Kimiaki, Vu Tuan, Weiss Michael D, Zajda Małgorzata, Bloemers Jos, Boroojerdi Babak, Brock Melissa, de la Borderie Guillemette, Duda Petra W, Vanderkelen Mark, Leite M Isabel
机构信息
Department of Neurology, UNC School of Medicine, The University College of North Carolina at Chapel Hill, 2200 Houpt Building, CB#7025, 170 Manning Drive, Chapel Hill, NC 27599-7025, USA.
Service de Neurologie, Hospital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France.
出版信息
Ther Adv Neurol Disord. 2024 Apr 17;17:17562864241243186. doi: 10.1177/17562864241243186. eCollection 2024.
BACKGROUND
Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments.
OBJECTIVES
To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population.
DESIGN
Ongoing, multicenter, phase III open-label extension (OLE) study.
METHODS
Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score.
RESULTS
In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11-4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening ( = 52, 26%) and COVID-19 ( = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline -6.06 [-7.09, -5.03]) and were sustained through to Week 60 (-6.04 [-7.21, -4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (-6.46 [-8.19, -4.72]), and were sustained through to Week 60 (-6.51 [-8.37, -4.65]). Consistent results were observed in other efficacy endpoints.
CONCLUSION
Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871).
背景
全身型重症肌无力（gMG）是一种慢性、不可预测的疾病，治疗负担和疾病负担都很高，需要更有效且耐受性良好的治疗方法。
目的
评估zilucoplan在轻度至重度、乙酰胆碱受体自身抗体阳性（AChR+）的gMG患者群体中的长期安全性、耐受性和疗效。
设计
正在进行的多中心III期开放标签扩展（OLE）研究。
方法
符合条件的患者已完成一项合格的随机、安慰剂对照的II期或III期zilucoplan研究，并接受每日自行皮下注射0.3mg/kg的zilucoplan。主要终点是治疗中出现的不良事件（TEAE）的发生率。次要疗效终点包括重症肌无力日常生活活动（MG-ADL）评分相对于基线的变化。
结果
共有200名患者入组。截至截止日期（2022年9月8日），RAISE-XT中患者接受zilucoplan的中位（范围）暴露时间为1.2（0.11-4.45）年。OLE基线时的平均年龄为53.3岁。共有188名（94%）患者发生了TEAE，最常见的是MG病情恶化（n=52，26%）和新冠病毒病（n=49，25%）。在母研究中接受0.3mg/kg zilucoplan的患者中，MG-ADL评分在第24周持续进一步改善（从双盲基线的最小二乘均值变化[95%置信区间]为-6.06[-7.09，-5.03]），并持续到第60周（-6.04[-7.21，-4.87]）。在母研究中从安慰剂转换过来的患者中，转换为zilucoplan后的第一周观察到MG-ADL评分迅速改善；在转换后12周的第24周观察到进一步改善（-6.46[-8.19，-4.72]），并持续到第60周（-6.51[-8.37，-4.65]）。在其他疗效终点也观察到了一致的结果。
结论
Zilucoplan显示出良好的长期安全性、耐受性，并且在第60周前疗效持续，在广泛的AChR+ gMG患者群体中具有一致的益处。未来的分析将提供更多长期数据。
试验注册
ClinicalTrials.gov标识符：NCT04225871（https://clinicaltrials.gov/ct2/show/NCT04225871）
Zotero 插件