"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"

作者全名："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; Zhao, Qianhua; Guo, Qihao; Zhou, Yongtao; Li, Yi; Jiang, Lijun; Ren, Wenwei; Ouyang, Yingjun; Wang, Yan; Liu, Shuai; Jia, Jianjun; Zhang, Nan; Liu, Zhonglin; He, Raoli; Feng, Tingyi; Lu, Wenhui; Tang, Huidong; Gao, Ping; Zhang, Yingchun; Chen, Lanlan; Wang, Lei; Yin, You; Xu, Qun; Xiao, Jinsong; Cong, Lin; Cheng, Xi; Zhang, Hui; Gao, Dan; Xia, Minghua; Lian, Tenghong; Peng, Guoping; Zhang, Xu; Jiao, Bin; Hu, Hua; Chen, Xueyan; Guan, Yihui; Cui, Ruixue; Huang, Qiu; Xin, Xianliang; Chen, Hongjian; Ding, Yu; Zhang, Jing; Feng, Teng; Cantillon, Marc; Chen, Kewei; Cummings, Jeffrey L.; Ding, Jian; Geng, Meiyu; Zhang, Zhenxin"

作者地址："[Xiao, Shifu; Wang, Tao] Shanghai Jiao Tong Univ, Dept Geriatr Psychiat, Shanghai Mental Hlth Ctr, Sch Med, Shanghai, Peoples R China; [Xiao, Shifu; Wang, Tao] Shanghai Jiao Tong Univ, Alzheimers Dis & Related Disorders Ctr, 600 South Wan Ping Rd, Shanghai 200030, Peoples R China; [Chan, Piu; Zhou, Yongtao] Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China; [Hong, Zhen; Zhao, Qianhua; Guo, Qihao; Guan, Yihui; Geng, Meiyu] Fudan Univ, Huashan Hosp, Shanghai, Peoples R China; [Wang, Shuzhen; Li, Yi] Shandong Univ, Qilu Hosp, Jinan, Peoples R China; [Kuang, Weihong; Jiang, Lijun] Sichuan Univ, West China Hosp, Chengdu, Peoples R China; [He, Jincai; Ren, Wenwei] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China; [Pan, Xiaoping; Ouyang, Yingjun] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Guangzhou, Peoples R China; [Zhou, Yuying; Ji, Yong; Wang, Yan; Liu, Shuai] Nankai Univ, Tianjin Huanhu Hosp, Huanhu Hosp, Tianjin, Peoples R China; [Wang, Luning; Jia, Jianjun] Peoples Liberat Army Gen Hosp, Dept Geriatr Neurol, Beijing, Peoples R China; [Cheng, Yan; Zhang, Nan] Tianjin Med Univ Gen Hosp, Dept Neurol, Tianjin, Peoples R China; [Peng, Ying; Liu, Zhonglin] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Peoples R China; [Ye, Qinyong; He, Raoli] Fujian Med Univ, Union Hosp, Fuzhou, Peoples R China; [Wang, Xiaoping; Wu, Yuncheng; Feng, Tingyi] Shanghai Jiao Tong Univ, Sch Med, Dept Neurol, Shanghai Gen Hosp, Shanghai, Peoples R China; [Qu, Qiumin; Lu, Wenhui] Xi An Jiao Tong Univ, Dept Neurol, Affiliated Hosp 1, Xian, Peoples R China; [Chen, Shengdi; Tang, Huidong] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Neurol, Shanghai, Peoples R China; [Li, Shuhua; Gao, Ping] Beijing Hosp, Beijing, Peoples R China; [Chen, Wei; Zhang, Yingchun] Zhejiang Univ, Sch Med, Dept Psychiat, Sir Run Run Shaw Hosp, Hangzhou, Peoples R China; [Chen, Wei; Zhang, Yingchun] Key Lab Med Neurobiol Zhejiang Prov, Hangzhou, Peoples R China; [Xu, Jun; Chen, Lanlan] Northern Jiangsu Peoples Hosp, Yangzhou, Jiangsu, Peoples R China; [Peng, Dantao; Wang, Lei] China Japan Friendship Hosp, Dept Neurol, Beijing, Peoples R China; [Zhao, Zhongxin; Yin, You] Shanghai Changzheng Hosp, Shanghai, Peoples R China; [Li, Yansheng; Xu, Qun] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai, Peoples R China; [Zhang, Junjian; Xiao, Jinsong] Wuhan Univ, Zhongnan Hosp, Dept Neurol, Wuhan, Peoples R China; [Du, Yifeng; Cong, Lin] Shandong Univ, Shandong Prov Hosp, Jinan, Peoples R China; [Chen, Weixian; Cheng, Xi] Jiangsu Prov Peoples Hosp, Nanjing, Peoples R China; [Fan, Dongsheng; Zhang, Hui] Peking Univ Third Hosp, Beijing, Peoples R China; [Yan, Yong; Gao, Dan] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Liu, Xiaowei; Xia, Minghua] Wuxi Mental Hlth Ctr, Dept Geriatr Psychiat, Wuxi, Jiangsu, Peoples R China; [Zhang, Wei; Lian, Tenghong] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China; [Luo, Benyan; Peng, Guoping] Zhejiang Univ, Sch Med, Affiliated Hosp1, Hangzhou, Peoples R China; [Wu, Wenyuan; Zhang, Xu] Tongji Univ, Tongji Hosp, Shanghai, Peoples R China; [Shen, Lu; Jiao, Bin] Cent South Univ, Xiangya Hosp, Changsha, Peoples R China; [Liu, Chunfeng; Hu, Hua] Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China; [Mao, Peixian; Chen, Xueyan] Capital Med Univ, Beijing An Ding Hosp, Beijing, Peoples R China; [Wang, Qiumei; Cui, Ruixue; Zhang, Zhenxin] Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China; [Huang, Qiu] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai, Peoples R China; [Xin, Xianliang; Chen, Hongjian; Ding, Yu; Zhang, Jing; Feng, Teng; Cantillon, Marc] Shanghai Green Valley Pharmaceut Co Ltd, 421 Niudun Rd, Shanghai, Peoples R China; [Chen, Kewei] Banner Alzheimers Inst, Phoenix, AZ USA; [Cummings, Jeffrey L.] Univ Nevada, Dept Brain Hlth, Sch Integrated Hlth Sci, Chamberrs Grundy Ctr Transformat Neurosci, Las Vegas, NV 89154 USA; [Ding, Jian] Chinese Acad Sci, Shanghai Inst Mat Medica, State Key Lab Drug Res, 555 Chong Zhi Rd, Nevada, Peoples R China"

通信作者："Xiao, SF (corresponding author), Shanghai Jiao Tong Univ, Dept Geriatr Psychiat, Shanghai Mental Hlth Ctr, Sch Med, Shanghai, Peoples R China.; Geng, MY (corresponding author), Fudan Univ, Huashan Hosp, Shanghai, Peoples R China.; Zhang, ZX (corresponding author), Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China."

来源：ALZHEIMERS RESEARCH & THERAPY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000630011200001

JCR分区：Q1

影响因子：9

年份：2021

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Sodium oligomannate; Efficacy; Safety; Alzheimer's disease; Clinical trial

摘要："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."

基金机构："Shanghai Green Valley Pharmaceuticals (SHGV); National Science and Technology Major Project for Investigational New Drugs [2011ZX09101-003-01, 2015ZX09101003, 2018ZX09711002-015]"

基金资助正文："This trial was funded by the Shanghai Green Valley Pharmaceuticals (SHGV) and National Science and Technology Major Project for Investigational New Drugs (2011ZX09101-003-01, 2015ZX09101003, 2018ZX09711002-015)."