Rozanolixizumab 在中度至重度全身性重症肌无力中的疗效和安全性：一项 2 期随机对照试验。
Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial.
机构信息
From Toronto General Hospital (V.B.), University Health Network, University of Toronto, Canada; Department of Neurology (M. Benatar), Miller School of Medicine, University of Miami, FL; Department of Neurology (H.A.), Aarhus University Hospital; Department of Neurology, Rigshospitalet (J.V.), University of Copenhagen, Denmark; UCB Pharma (M. Brock), Raleigh, NC; UCB Pharma (B.G., P.K., F.W.), Monheim-am-Rhein, Germany; iMed Communications (L.G.), Macclesfield, UK; and Neuromuscular Reference Centre, Department of Neurology (P.V.d.B.), University Hospital Saint-Luc, University of Louvain, Brussels, Belgium.
出版信息
Neurology. 2021 Feb 9;96(6):e853-e865. doi: 10.1212/WNL.0000000000011108. Epub 2020 Nov 20.
OBJECTIVE
To explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG).
METHODS
In this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1-29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29-43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44-99). Primary endpoint was change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints were change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores and safety.
RESULTS
Forty-three patients were randomized (rozanolixizumab 21, placebo 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo was as follows: QMG (LS mean -1.8 vs -1.2, difference -0.7, 95% upper confidence limit [UCL] 0.8; = 0.221; not statistically significant), MG-ADL (LS mean -1.8 vs -0.4, difference -1.4, 95% UCL -0.4), and MGC (LS mean -3.1 vs -1.2, difference -1.8, 95% UCL 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab 57%, placebo 14%).
CONCLUSION
Whereas change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422).
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that for patients with gMG, rozanolixizumab is well-tolerated, but did not significantly improve QMG score.
目的
探索皮下（SC）rozanolixizumab（一种抗新生 Fc 受体的人源化单克隆抗体）在全身性重症肌无力（gMG）患者中的临床疗效和安全性。
方法
在这项 2a 期、随机、双盲、安慰剂对照、2 期、多中心试验（NCT03052751）中，患者在第 1 期（第 1-29 天）按 1:1 比例随机分为rozanolixizumab 7mg/kg 或安慰剂 3 次每周一次（Q1W）SC 输注。在第 2 期（第 29-43 天），患者重新随机分为 rozanolixizumab 7mg/kg 或 4mg/kg（3 次 Q1W SC 输注），随后进行观察期（第 44-99 天）。主要终点是从基线到第 29 天的定量重症肌无力（QMG）评分变化。次要终点是从基线到第 29 天的 MG-日常生活活动（MG-ADL）和 MG 综合（MGC）评分以及安全性的变化。
结果
43 名患者被随机分配（rozanolixizumab 21 名，安慰剂 22 名[第 1 期]）。与安慰剂相比，rozanolixizumab 从基线到第 29 天的最小二乘（LS）均值变化如下：QMG（LS 均值-1.8 对-1.2，差值-0.7，95%置信上限[UCL]为 0.8；=0.221；无统计学意义），MG-ADL（LS 均值-1.8 对-0.4，差值-1.4，95%UCL-0.4）和 MGC（LS 均值-3.1 对-1.2，差值-1.8，95%UCL 0.4）评分。在第 2 期，rozanolixizumab 7mg/kg 继续改善疗效。第 1 期最常见的不良事件是头痛（rozanolixizumab 57%，安慰剂 14%）。
结论
虽然 QMG 从基线的变化没有统计学意义，但总体数据表明，rozanolixizumab 可能为 gMG 患者提供临床获益，且总体耐受性良好。第 3 阶段评估正在进行中（NCT03971422）。
证据分类
这项研究提供了 I 级证据，表明对于 gMG 患者，rozanolixizumab 耐受性良好，但并未显著改善 QMG 评分。
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