Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial
Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial
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DOI：
10.1038/s41591-021-01455-x
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发表时间：
2021-08-12
期刊：
影响因子：
82.9
通讯作者：
Haeberlein, Samantha Budd
中科院分区：
文献类型：
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作者：
Dam, Tien;Boxer, Adam L.;Haeberlein, Samantha Budd
在第二阶段护照研究中，抗TAU抗体gosuranemab的治疗没有显示出近核麻痹参与者的临床益处，这表明N端Tau中和不会转化为临床功效。 ，为期52周的研究（No。NCT03068468）评估了一种抗TAU单克隆抗体的Gosuranemab，用于治疗进行性上核瘫痪（PSP）。总共将486名剂量的参与者分配给Gosuranemab（n = 321）或安慰剂（n = 165）。在Gosuranemab和安慰剂之间第52周的PSP评级量表得分的调整后平均变化（10.4对10.4对10.6对10.6，P = 0.85，主要终终点）或次级终点点上，未证明疗效扩大。 Gosuranemab的脑脊液中未结合的N末端TAU降低了98％，安慰剂随着安慰剂的增长11％（p <0.0001）。两组之间不良事件和死亡的发生率相似。这项功能齐全的研究表明，N端Tau中和不能转化为临床功效。
In the phase 2 PASSPORT study, treatment with the anti-tau antibody gosuranemab did not show clinical benefit in participants with supranuclear palsy, suggesting that N-terminal tau neutralization does not translate into clinical efficacy.A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P < 0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy.