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, Shanghai Jiao Tong University School of Medicine
Piu Chan, Xuanwu Hospital, Capital Medical University
Tao Wang, Shanghai Jiao Tong University School of Medicine
Zhen Hong, Fudan University
Shuzhen Wang, Qilu Hospital of Shandong University
Weihong Kuang, West China School of Medicine/West China Hospital of Sichuan University
Jincai He, The First Affiliated Hospital of Wenzhou Medical University
Xiaoping Pan, South China University of Technology
Yuying Zhou, Nankai University
Yong Ji, Nankai University
Luning Wang, General Hospital of People's Liberation Army
Yan Cheng, Tianjin Medical University
Ying Peng, Sun Yat-Sen University
Qinyong Ye, Fujian Medical University
Xiaoping Wang, Shanghai Jiao Tong University School of Medicine
Yuncheng Wu, Shanghai Jiao Tong University School of Medicine
Qiumin Qu, The First Hospital of Xian Jiaotong University
Shengdi Chen, Shanghai Jiao Tong University School of Medicine
Shuhua Li, Beijing Hospital
Wei Chen, Sir Run Run Shaw Hospital
Jun Xu, Northern Jiangsu People's Hospital
Dantao Peng, China-Japan Friendship Hospital
Zhongxin Zhao, Changzheng Hospital
Yansheng Li, Shanghai Jiao Tong University School of Medicine
Junjian Zhang, Zhongnan Hospital of Wuhan University
Yifeng Du, Shandong University
Weixian Chen, Jiangsu Province People’s Hospital
Dongsheng Fan, Peking University Third Hospital
Yong Yan, The First Affiliated Hospital of Chongqing Medical University
Xiaowei Liu


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, NCT02293915. Registered on November 19, 2014