Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Alzheimer's Disease and Related Disorders Center, Shanghai Jiaotong University, 600 South Wan Ping Road, Shanghai, 200030, China.
Alzheimers Res Ther. 2021 Mar 17;13(1):62. doi: 10.1186/s13195-021-00795-7.
New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.
We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored.
A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.
GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.
ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.
阿尔茨海默病（AD）急需新的治疗方法。低聚甘露糖（GV-971）是一种源自海洋的寡糖，具有新颖的作用机制。GV-971 的首个 3 期临床试验已在中国完成。
我们在中国进行了一项 3 期、双盲、安慰剂对照试验，评估 GV-971 的疗效和安全性。参与者被随机分配至安慰剂或 GV-971（900mg）治疗 36 周。主要结局是阿尔茨海默病评估量表（ADAS-cog12）12 项认知子量表的基线变化药物-安慰剂差值。次要终点是药物-安慰剂在临床医生访谈的变化印象与照顾者输入（CIBIC+）、阿尔茨海默病合作研究-日常生活活动（ADCS-ADL）量表和神经精神问卷（NPI）上的差异。监测安全性和耐受性。
共有 818 名参与者被随机分组：408 名接受 GV-971 治疗，410 名接受安慰剂治疗。GV-971 治疗在每个测量时间点均显著优于安慰剂，在第 4 周访视时即可测量，并贯穿整个试验。治疗 36 周后，两组间的基线变化差异为 -2.15 分（95%置信区间，-3.07 至 -1.23；p<0.0001；效应大小 0.531）。治疗后出现的不良事件发生率在活性治疗组和安慰剂组之间相当（73.9%，75.4%）。GV-971 组发生 2 例死亡，确定与药物无关。
GV-971 显著改善认知功能，在 36 周试验的所有观察期均持续改善。GV-971 安全且耐受良好。
ClinicalTrials.gov，NCT02293915。于 2014 年 11 月 19 日注册。
