A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia

作者：Xiao, Shifu; Chan, Piu; Wang, Tao; Hong, Zhen; Wang, Shuzhen; Kuang, Weihong; He, Jincai; Pan, Xiaoping; Zhou, Yuying; Ji, Yong; Wang, Luning; Cheng, Yan; Peng, Ying; Ye, Qinyong; Wang, Xiaoping; Wu, Yuncheng; Qu, Qiumin; Chen, Shengdi; Li, Shuhua; Chen, Wei; Xu, Jun; Peng, Dantao; Zhao, Zhongxin; Li, Yansheng; Zhang, Junjian; Du, Yifeng; Chen, Weixian; Fan, Dongsheng; Yan, Yong; Liu, Xiaowei; Zhang, Wei; Luo, Benyan; Wu, Wenyuan; Shen, Lu; Liu, Chunfeng; Mao, Peixian; Wang, Qiumei

来源：Alzheimers Research & Therapy, 2021, 13(1): 62.

DOI：10.1186/s13195-021-00795-7

• Sodium oligomannate
• Efficacy
• Safety
• Alzheimer's disease
• Clinical trial

Background: 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. @@@ Methods: 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. @@@ Results: 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. @@@ Conclusions: 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.

• 单位
  同济大学; 上海材料研究所; 浙江大学; 中国医学科学院北京协和医院; 武汉大学; 北京大学; 苏州大学; 西安交通大学; 复旦大学; 山东大学; 南开大学; 中山大学; 上海交通大学; 四川大学; 中国科学院