PDF(Pubmed)
Abstract：
UNASSIGNED: Blood biomarkers are proposed as a diagnostic alternative to amyloid PET or cerebrospinal fluid (CSF) analyses for the diagnosis of Alzheimer\'s disease (AD). Relatively little is known of the natural history of patients identified by different blood biomarkers.
UNASSIGNED: To identify patients with elevated plasma phosphorylated tau (pTau)181 from a prior Phase 2a trial, and explore the natural histories of their clinical progression, and potential efficacy of Xanamem, a selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these patients.
UNASSIGNED: A prespecified, double-blind analysis was conducted in 72 participants with clinically diagnosed AD and available plasma samples from baseline and Week 12 of the \"XanADu\" Phase 2a trial of Xanamem versus placebo. The analysis prespecified plasma pTau181 > median to identify patients more likely to have AD (\"H\", > 6.74 pg/mL, n = 34). Cohen\'s d (d) of≥0.2 defined potential clinical significance.
UNASSIGNED: In the placebo group, H patients showed greater clinical progression compared to L patients (pTau181≤median) on ADCOMS (d = 0.55, p < 0.001), CDR-SB (d = 0.63, p < 0.001), MMSE (d = 0.52, p = 0.12), and ADAS-Cog14 (d = 0.53, p = 0.19). In H patients, a potentially clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS mean difference 0.6 units, d = 0.41, p = 0.09) and Neuropsychological Test Battery (NTB; LS mean difference 1.8 units, d = 0.26, p = 0.48) but not ADCOMS or ADAS-Cog14.
UNASSIGNED: This trial demonstrates that elevated plasma pTau181 identifies participants more likely to have progressive AD and is a suitable method for enrichment in AD clinical trials. Xanamem treatment showed evidence of potential clinically meaningful benefits.
UNASSIGNED: To identify patients with elevated plasma phosphorylated tau (pTau)181 from a prior Phase 2a trial, and explore the natural histories of their clinical progression, and potential efficacy of Xanamem, a selective inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these patients.
UNASSIGNED: A prespecified, double-blind analysis was conducted in 72 participants with clinically diagnosed AD and available plasma samples from baseline and Week 12 of the \"XanADu\" Phase 2a trial of Xanamem versus placebo. The analysis prespecified plasma pTau181 > median to identify patients more likely to have AD (\"H\", > 6.74 pg/mL, n = 34). Cohen\'s d (d) of≥0.2 defined potential clinical significance.
UNASSIGNED: In the placebo group, H patients showed greater clinical progression compared to L patients (pTau181≤median) on ADCOMS (d = 0.55, p < 0.001), CDR-SB (d = 0.63, p < 0.001), MMSE (d = 0.52, p = 0.12), and ADAS-Cog14 (d = 0.53, p = 0.19). In H patients, a potentially clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS mean difference 0.6 units, d = 0.41, p = 0.09) and Neuropsychological Test Battery (NTB; LS mean difference 1.8 units, d = 0.26, p = 0.48) but not ADCOMS or ADAS-Cog14.
UNASSIGNED: This trial demonstrates that elevated plasma pTau181 identifies participants more likely to have progressive AD and is a suitable method for enrichment in AD clinical trials. Xanamem treatment showed evidence of potential clinically meaningful benefits.
摘要：
■血液生物标志物被提议作为淀粉样蛋白PET或脑脊液（CSF）分析的诊断替代方案，用于诊断阿尔茨海默病（AD）。对通过不同血液生物标志物鉴定的患者的自然史知之甚少。
■为了从先前的2a期试验中确定血浆磷酸化tau（pTau）181升高的患者，探索其临床进展的自然史，和Xanamem的潜在功效，这些患者的11β-羟基类固醇脱氢酶1型（11β-HSD1）的选择性抑制剂。
■预先指定的，我们对72例临床诊断为AD的参与者进行了双盲分析,并从基线和Xanamem与安慰剂的XanADu2a期试验第12周获得了血浆样本.分析预设血浆pTau181>中位数，以确定更有可能患有AD的患者(“H”，>6.74pg/mL,n=34）。科恩的d(d)≥0.2定义的潜在临床意义。
■在安慰剂组中，在ADCOMS上，与L患者（pTau181≤中位数）相比，H患者表现出更大的临床进展（d=0.55，p<0.001），CDR-SB（d=0.63，p<0.001），MMSE（d=0.52，p=0.12），和ADAS-Cog14（d=0.53，p=0.19）。在H患者中，与安慰剂相比，在CDR-SB中观察到潜在的临床意义的Xanamem治疗效果（LS平均差0.6单位，d=0.41，p=0.09)和神经心理学测验(NTB；LS平均差1.8个单位，d=0.26，p=0.48），但不是ADCOMS或ADAS-Cog14。
■该试验表明，升高的血浆pTau181可识别出更有可能患有进行性AD的参与者，并且是在AD临床试验中进行富集的合适方法。Xanamem治疗显示了潜在的临床意义益处的证据。
■为了从先前的2a期试验中确定血浆磷酸化tau（pTau）181升高的患者，探索其临床进展的自然史，和Xanamem的潜在功效，这些患者的11β-羟基类固醇脱氢酶1型（11β-HSD1）的选择性抑制剂。
■预先指定的，我们对72例临床诊断为AD的参与者进行了双盲分析,并从基线和Xanamem与安慰剂的XanADu2a期试验第12周获得了血浆样本.分析预设血浆pTau181>中位数，以确定更有可能患有AD的患者(“H”，>6.74pg/mL,n=34）。科恩的d(d)≥0.2定义的潜在临床意义。
■在安慰剂组中，在ADCOMS上，与L患者（pTau181≤中位数）相比，H患者表现出更大的临床进展（d=0.55，p<0.001），CDR-SB（d=0.63，p<0.001），MMSE（d=0.52，p=0.12），和ADAS-Cog14（d=0.53，p=0.19）。在H患者中，与安慰剂相比，在CDR-SB中观察到潜在的临床意义的Xanamem治疗效果（LS平均差0.6单位，d=0.41，p=0.09)和神经心理学测验(NTB；LS平均差1.8个单位，d=0.26，p=0.48），但不是ADCOMS或ADAS-Cog14。
■该试验表明，升高的血浆pTau181可识别出更有可能患有进行性AD的参与者，并且是在AD临床试验中进行富集的合适方法。Xanamem治疗显示了潜在的临床意义益处的证据。
