Alzheimer’s Research & Therapy (Mar 2021)

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

  • Shifu Xiao,
  • Piu Chan,
  • Tao Wang,
  • Zhen Hong,
  • Shuzhen Wang,
  • Weihong Kuang,
  • Jincai He,
  • Xiaoping Pan,
  • Yuying Zhou,
  • Yong Ji,
  • Luning Wang,
  • Yan Cheng,
  • Ying Peng,
  • Qinyong Ye,
  • Xiaoping Wang,
  • Yuncheng Wu,
  • Qiumin Qu,
  • Shengdi Chen,
  • Shuhua Li,
  • Wei Chen,
  • Jun Xu,
  • Dantao Peng,
  • Zhongxin Zhao,
  • Yansheng Li,
  • Junjian Zhang,
  • Yifeng Du,
  • Weixian Chen,
  • Dongsheng Fan,
  • Yong Yan,
  • Xiaowei Liu,
  • Wei Zhang,
  • Benyan Luo,
  • Wenyuan Wu,
  • Lu Shen,
  • Chunfeng Liu,
  • Peixian Mao,
  • Qiumei Wang,
  • Qianhua Zhao,
  • Qihao Guo,
  • Yongtao Zhou,
  • Yi Li,
  • Lijun Jiang,
  • Wenwei Ren,
  • Yingjun Ouyang,
  • Yan Wang,
  • Shuai Liu,
  • Jianjun Jia,
  • Nan Zhang,
  • Zhonglin Liu,
  • Raoli He,
  • Tingyi Feng,
  • Wenhui Lu,
  • Huidong Tang,
  • Ping Gao,
  • Yingchun Zhang,
  • Lanlan Chen,
  • Lei Wang,
  • You Yin,
  • Qun Xu,
  • Jinsong Xiao,
  • Lin Cong,
  • Xi Cheng,
  • Hui Zhang,
  • Dan Gao,
  • Minghua Xia,
  • Tenghong Lian,
  • Guoping Peng,
  • Xu Zhang,
  • Bin Jiao,
  • Hua Hu,
  • Xueyan Chen,
  • Yihui Guan,
  • Ruixue Cui,
  • Qiu Huang,
  • Xianliang Xin,
  • Hongjian Chen,
  • Yu Ding,
  • Jing Zhang,
  • Teng Feng,
  • Marc Cantillon,
  • Kewei Chen,
  • Jeffrey L. Cummings,
  • Jian Ding,
  • Meiyu Geng,
  • Zhenxin Zhang

DOI
https://doi.org/10.1186/s13195-021-00795-7
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 11

Abstract

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Abstract 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. Trial registration ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014

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