Neuroscience, AbbVie Inc., North Chicago, IL 60064, USA.
Data and Statistical Sciences, AbbVie Inc., North Chicago, IL 60064, USA.
Brain. 2023 Jun 1;146(6):2275-2284. doi: 10.1093/brain/awad024.
Tau accumulation in patients with Alzheimer's disease tracks closely with cognitive decline and plays a role in the later stages of disease progression. This phase 2 study evaluated the safety and efficacy of tilavonemab, an anti-tau monoclonal antibody, in patients with early Alzheimer's disease. In this 96-week, randomized, double-blind, placebo-controlled study (NCT02880956), patients aged 55-85 years meeting clinical criteria for early Alzheimer's disease with a Clinical Dementia Rating-Global Score of 0.5, a Mini-Mental State Examination score of 22 to 30, a Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index score of ≤85, and a positive amyloid PET scan were randomized 1:1:1:1 to receive one of three doses of tilavonemab (300 mg, 1000 mg, or 2000 mg) or placebo via intravenous infusion every 4 weeks. The primary end point was the change from baseline up to Week 96 in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Safety evaluations included adverse event monitoring and MRI assessments. A total of 453 patients were randomized, of whom 337 were treated with tilavonemab (300 mg, n = 108; 1000 mg, n = 116; 2000 mg, n = 113) and 116 received placebo. Baseline demographics and disease characteristics were comparable across groups. The mean age was 71.3 (SD 7.0) years, 51.7% were female, and 96.5% were White. At baseline, the mean CDR-SB score was 3.0 (1.2), which worsened through Week 96 for all treatment groups. The least squares mean change from baseline at Week 96 in the CDR-SB score with tilavonemab was not significantly different compared with placebo [300 mg (n = 85): -0.07 (95% confidence interval, CI: -0.83 to 0.69); 1000 mg (n = 91): -0.06 (95% CI: -0.81 to 0.68); 2000 mg (n = 81): 0.16 (95% CI: -0.60 to 0.93); all P ≥ 0.05]. The incidence of any adverse event and MRI findings were generally comparable across groups. Tilavonemab was generally well tolerated but did not demonstrate efficacy in treating patients with early Alzheimer's disease. Further investigations of tilavonemab in early Alzheimer's disease are not warranted.
tau 蛋白在阿尔茨海默病患者中的积累与认知能力下降密切相关，并在疾病进展的后期阶段发挥作用。这项 2 期研究评估了靶向 tau 的单克隆抗体 tilavonemab 在早期阿尔茨海默病患者中的安全性和疗效。在这项为期 96 周、随机、双盲、安慰剂对照的研究（NCT02880956）中，年龄在 55-85 岁之间、符合早期阿尔茨海默病临床标准、临床痴呆评定量表总分为 0.5、简易精神状态检查量表评分为 22-30、重复神经心理状态评估量表-延迟记忆指数评分为 ≤85、且正电子发射断层扫描显示淀粉样蛋白阳性的患者，按 1:1:1:1 的比例随机分为四组，分别接受三种剂量的 tilavonemab（300mg、1000mg 或 2000mg）或安慰剂，每 4 周静脉输注一次。主要终点是从基线到第 96 周时临床痴呆评定量表-总和评分（CDR-SB）的变化。安全性评估包括不良事件监测和 MRI 评估。共 453 名患者被随机分组，其中 337 名接受 tilavonemab 治疗（300mg，n=108；1000mg，n=116；2000mg，n=113），116 名接受安慰剂治疗。各组的基线人口统计学和疾病特征具有可比性。平均年龄为 71.3（SD 7.0）岁，51.7%为女性，96.5%为白人。基线时，CDR-SB 评分平均为 3.0（1.2），所有治疗组在第 96 周时均恶化。与安慰剂相比，tilavonemab 治疗组第 96 周时 CDR-SB 评分的最小二乘均数变化无显著差异[300mg（n=85）：-0.07（95%置信区间，CI：-0.83 至 0.69）；1000mg（n=91）：-0.06（95%CI：-0.81 至 0.68）；2000mg（n=81）：0.16（95%CI：-0.60 至 0.93）；所有 P≥0.05]。各组不良事件和 MRI 发现的发生率通常相当。tilavonemab 总体耐受性良好，但未能证明其在治疗早期阿尔茨海默病患者中的疗效。因此，没有必要进一步研究 tilavonemab 在早期阿尔茨海默病中的应用。
