Shifu Xiao1,2, Piu Chan3, Tao Wang4,5, Zhen Hong6, Shuzhen Wang7, Weihong Kuang8, Jincai He9, Xiaoping Pan10, Yuying Zhou11, Yong Ji11, Luning Wang12, Yan Cheng13, Ying Peng14, Qinyong Ye15, Xiaoping Wang16, Yuncheng Wu16, Qiumin Qu17, Shengdi Chen18, Shuhua Li19, Wei Chen20, Jun Xu21, Dantao Peng22, Zhongxin Zhao23, Yansheng Li24, Junjian Zhang25, Yifeng Du26, Weixian Chen27, Dongsheng Fan28, Yong Yan29, Xiaowei Liu30, Wei Zhang31, Benyan Luo32, Wenyuan Wu33, Lu Shen34, Chunfeng Liu35, Peixian Mao36, Qiumei Wang37, Qianhua Zhao6, Qihao Guo6, Yongtao Zhou3, Yi Li7, Lijun Jiang8, Wenwei Ren9, Yingjun Ouyang10, Yan Wang11, Shuai Liu11, Jianjun Jia12, Nan Zhang13, Zhonglin Liu14, Raoli He15, Tingyi Feng16, Wenhui Lu17, Huidong Tang18, Ping Gao19, Yingchun Zhang20, Lanlan Chen21, Lei Wang22, You Yin23, Qun Xu24, Jinsong Xiao25, Lin Cong26, Xi Cheng27, Hui Zhang28, Dan Gao29, Minghua Xia30, Tenghong Lian31, Guoping Peng32, Xu Zhang33, Bin Jiao34, Hua Hu35, Xueyan Chen36, Yihui Guan6, Ruixue Cui37, Qiu Huang38, Xianliang Xin39, Hongjian Chen39, Yu Ding39, Jing Zhang39, Teng Feng39, Marc Cantillon39, Kewei Chen40, Jeffrey L Cummings41, Jian Ding42, Meiyu Geng43, Zhenxin Zhang44. 1. Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China. xiaoshifu@msn.com. 2. Alzheimer's Disease and Related Disorders Center, Shanghai Jiaotong University, 600 South Wan Ping Road, Shanghai, 200030, China. xiaoshifu@msn.com. 3. Xuanwu Hospital Capital Medical University, Beijing, China. 4. Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China. 5. Alzheimer's Disease and Related Disorders Center, Shanghai Jiaotong University, 600 South Wan Ping Road, Shanghai, 200030, China. 6. Huashan Hospital, Fudan University, Shanghai, China. 7. Qilu Hospital of Shandong University, Ji'nan, China. 8. West China Hospital of Sichuan University, Chengdu, China. 9. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 10. Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China. 11. Tianjin Huanhu Hospital, Huanhu Hospital Affiliated to Nankai University, Tianjin, China. 12. Department of Geriatric Neurology of PLA General Hospital, Beijing, China. 13. Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China. 14. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 15. Fujian Medical University Union Hospital, Fuzhou, China. 16. Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 17. Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 18. Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 19. Beijing Hospital, Beijing, China. 20. Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine and Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou, China. 21. Northern Jiangsu People's Hospital, Yangzhou, China. 22. Department of Neurology, China-Japan Friendship Hospital, Beijing, China. 23. Shanghai Changzheng Hospital, Shanghai, China. 24. Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 25. Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China. 26. Shandong Provinical Hospital affiliated to Shandong University, Ji'nan, China. 27. Jiangsu Province People's Hospital, Nanjing, China. 28. Peking University Third Hospital, Beijing, China. 29. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 30. Department of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China. 31. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 32. The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 33. Tongji Hospital of Tongji University, Shanghai, China. 34. Xiangya Hospital Central South University, Changsha, China. 35. The Second Affiliated Hospital of Soochow University, Suzhou, China. 36. Beijing An Ding Hospital, Capital Medical University, Beijing, China. 37. Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China. 38. Med-X Research Institution, Shanghai Jiao Tong University, Shanghai, China. 39. Shanghai Green Valley Pharmaceutical Co. Ltd., No. 421, Niudun Road, Shanghai, China. 40. Banner Alzheimer's Institute, Phoenix, AZ, USA. 41. Chamberrs-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, USA. 42. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Nevada, China. 43. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu chong zhi Road, Nevada, China. mygeng@simm.ac.cn. 44. Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Beijing, 100730, China. wuzhangzhenxin@163.com.
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.
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.
Authors: Stephen Salloway; Reisa Sperling; Nick C Fox; Kaj Blennow; William Klunk; Murray Raskind; Marwan Sabbagh; Lawrence S Honig; Anton P Porsteinsson; Steven Ferris; Marcel Reichert; Nzeera Ketter; Bijan Nejadnik; Volkmar Guenzler; Maja Miloslavsky; Daniel Wang; Yuan Lu; Julia Lull; Iulia Cristina Tudor; Enchi Liu; Michael Grundman; Eric Yuen; Ronald Black; H Robert Brashear Journal: N Engl J Med Date: 2014-01-23 Impact factor: 91.245
Authors: Napatsorn Saiyasit; Evan-Angelo R Butlig; Samantha D Chaney; Miranda K Traylor; Nanako A Hawley; Ryleigh B Randall; Hanna V Bobinger; Carl A Frizell; Franklin Trimm; Errol D Crook; Mike Lin; Benjamin D Hill; Joshua L Keller; Amy R Nelson Journal: Front Neurosci Date: 2022-06-29 Impact factor: 5.152