BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, rec...BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, reconstitute gut microbiota, and improve cognition in animal models of AD. A Phase 3 trial was conducted to assess efficacy and safety of GV-971. METHODS We conducted a Phase 3, double-blind placebo-controlled trial in patients with mild-to-moderate AD. Participants were randomized to receive 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(CIBIC+), Alzheimer′s Disease Cooperative Study-Activities of Daily Living(ADCS-ADL) scale, and Neuropsychiatric Inventory(NPI). The effect of GV-971 on the cerebral glucose metabolic rate was examined by 18 Fluorine-FDG PET in a subgroup. Safety and tolerability were monitored. RESULTS 818 participants were randomized, of which 408 were assigned to GV-971 and 410 to placebo. A significant drug-placebo difference in favor of GV-971 was present at each measurement time-point on the ADAS-Cog12. The difference between groups with regard to the 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 treatment. There was a trend towards benefit on CIBIC+(P=0.0588) but not on the ADCS-ADL(P=0.5712), NPI(P=0.8004), or the CMRglu. TEAE incidence77% and 76%, comparable between the two groups. Two deaths occurred in the GV-971 group;these were determined not to be related to GV-971. CONCLUSION GV-971 demonstrated significant efficacy in improving cognition and showed sustained improvement across al observation periods. GV-971 was safe and well tolerated.展开更多
文摘BACKGROUND New therapies are urgently needed for Alzheimer disease(AD). Sodium oligomannate(GV-971) is a marine-derived oligosaccharide that has been shown to decrease amyloid deposition, reduce neuroinflammation, reconstitute gut microbiota, and improve cognition in animal models of AD. A Phase 3 trial was conducted to assess efficacy and safety of GV-971. METHODS We conducted a Phase 3, double-blind placebo-controlled trial in patients with mild-to-moderate AD. Participants were randomized to receive 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(CIBIC+), Alzheimer′s Disease Cooperative Study-Activities of Daily Living(ADCS-ADL) scale, and Neuropsychiatric Inventory(NPI). The effect of GV-971 on the cerebral glucose metabolic rate was examined by 18 Fluorine-FDG PET in a subgroup. Safety and tolerability were monitored. RESULTS 818 participants were randomized, of which 408 were assigned to GV-971 and 410 to placebo. A significant drug-placebo difference in favor of GV-971 was present at each measurement time-point on the ADAS-Cog12. The difference between groups with regard to the 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 treatment. There was a trend towards benefit on CIBIC+(P=0.0588) but not on the ADCS-ADL(P=0.5712), NPI(P=0.8004), or the CMRglu. TEAE incidence77% and 76%, comparable between the two groups. Two deaths occurred in the GV-971 group;these were determined not to be related to GV-971. CONCLUSION GV-971 demonstrated significant efficacy in improving cognition and showed sustained improvement across al observation periods. GV-971 was safe and well tolerated.
