A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CRENEZUMAB IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CRENEZUMAB IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE
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一项随机、双盲、安慰剂对照的 2 期研究，旨在评估 Crenezumab 对轻度至中度阿尔茨海默病患者的疗效和安全性
DOI：
10.1016/j.jalz.2014.04.450
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Robert Paul
中科院分区：
文献类型：
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作者：
J. Cummings;W. Cho;M. Ward;M. Friesenhahn;F. Brunstein;L. Honigberg;D. Clayton;Deborah L. Mortensen;C. Ho;Robert Paul
研究背景Crenezumab是一种人源化的抗abeta单克隆抗体，用于治疗阿尔茨海默病（Alzheimer disease，AD）。Crenezumab已经在2期临床研究中进行了评估，该研究旨在评估其在轻度至中度AD患者中的疗效和安全性。MethodsThe研究在50 - 80岁的患者中进行，这些患者被诊断为轻度至中度AD，筛选MMSE评分为18-26分。共有433名患者以2：1的比例（活性药物与安慰剂）随机接受crenezumab或匹配的安慰剂治疗68周。184例患者每2周一次接受300 mg研究药物SC注射，247例患者每4周一次接受15 mg/kg研究药物IV输注。随机化按ApoE 4状态（携带者与非携带者）、MMSE评分（≤ 21与> 21）、MMSE评分（≤ 21与> 21）和MMSE评分（≤ 21与> 21）分层。（21）研究中心。共同主要疗效结局指标为ADAS-Cog 12和CDR-12评分从基线至第73周的变化。次要疗效结局指标为ADCS-ADL评分从基线至第73周的变化。使用重复测量分析的混合模型对研究终点的治疗差异进行统计分析。通过监测不良事件（AE），临床实验室评价，MRI评价（ARIA-E和ARIA-H事件）和immunogene.ResultsThe ADAS-Cog 12，CDR-ESTA和ADCS-ADL终点以及安全性数据进行评估，并discussedConclusionsThis临床试验的目的是提供一个评估的疗效和安全性crenezumab在AD患者轻度至中度痴呆。
BackgroundCrenezumab is a humanized anti-abeta monoclonal antibody in development for the treatment of Alzheimer disease (AD). Crenezumab has been evaluated in a phase 2 clinical study designed to assess its efficacy and safety in patients with mild to moderate AD.MethodsThe study was conducted in patients 50− 80 years of age who were diagnosed with mild to moderate AD with a screening MMSE score of 18-26 points. A total of 433 patients were randomized at a 2: 1 ratio (active to placebo) to receive either crenezumab or matching placebo for 68 weeks. 184 patients received 300 mg of study drug as a SC injection every 2 weeks and 247 patients received 15mg/kg of study drug as an IV infusion every 4 weeks. Randomization was stratified by ApoE4 status (carrier vs. non-carrier), MMSE score (≤ 21 vs.> 21), and study site. The co-primary efficacy outcome measures were the changes in the ADAS-Cog12 and CDR-SOB scores from baseline to Week 73. The secondary efficacy outcome measure was the change in the ADCS-ADL score from baseline to Week 73. A mixed model for repeated measures analysis was used for statistical analysis of treatment differences at study endpoints. Safety was assessed by monitoring adverse events (AEs), clinical laboratory evaluations, MRI evaluations (ARIA-E and ARIA-H events) and immunogenicity.ResultsThe ADAS-Cog12, CDR-SOB, and ADCS-ADL endpoints as well as safety data will be presented and discussedConclusionsThis clinical trial was designed to provide an evaluation of the efficacy and safety of crenezumab in AD patients with mild to moderate dementia.