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-Reference-Cited by-同舟云学术

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

Published:2021-03-17 Issue:1 Volume:13 Page:
ISSN:1758-9193
Container-title:Alzheimer's Research & Therapy
language:en
Short-container-title:Alz Res Therapy

Author:

Xiao Shifu^ORCID,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

Abstract

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, NCT02293915. Registered on November 19, 2014

Funder

National Science and Technology Major Project for Investigational New Drugs

Publisher

Springer Science and Business Media LLC

Subject

Cognitive Neuroscience,Neurology (clinical),Neurology

Link

http://link.springer.com/content/pdf/10.1186/s13195-021-00795-7.pdf

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