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

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-blin...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967962/
https://www.ncbi.nlm.nih.gov/pubmed/33731209
http://dx.doi.org/10.1186/s13195-021-00795-7
Descripción
Sumario: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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-021-00795-7.

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