Stephen Salloway 1 , Gad A Marshall 2 , Ming Lu 3 , H Robert Brashear 4 Show Affiliations »
Abstract
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BACKGROUND: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody directed at lowering the cerebral Aβ deposit in Alzheimer's disease (AD). OBJECTIVE: This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of bapineuzumab in patients with the mild-to-moderate AD . METHODS: Patients (58-78 years ) who completed either of two randomized, placebo-controlled, doubleblind studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose)) entered the OLE . Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study 201 and bapineuzumab IV in OLE (placebo/bapi ). RESULTS: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject (n=85) and AE (n=30 ). Mean (SD ) bapineuzumab exposure was 2.9 (1.90) years. There were no significant differences for efficacy endpoints (AD Assessment Scale-cognitive subscale [ADAS-Cog], Disability Assessment for Dementia [DAD] and MMSE scores ) between the bapi/bapi and placebo/bapi groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) occurred in 22 (11.3%) patients. The most common TEAEs (>20% patients) were fall, agitation and urinary tract infection with similar incidences between bapi/bapi and placebo/bapi groups. CONCLUSION: No significant difference was seen in cognitive and functional decline between early and delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed to death events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
RCT Entities: Population
Interventions
Outcomes
BACKGROUND: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody directed at lowering the cerebral Aβ deposit in Alzheimer's disease (AD ). OBJECTIVE: This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of bapineuzumab in patients with the mild-to-moderate AD . METHODS: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblind studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose)) entered the OLE. Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi /bapi ); and placebo in Study 201 and bapineuzumab IV in OLE (placebo/bapi ). RESULTS: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject (n=85) and AE (n=30). Mean (SD) bapineuzumab exposure was 2.9 (1.90) years. There were no significant differences for efficacy endpoints (AD Assessment Scale-cognitive subscale [ADAS-Cog], Disability Assessment for Dementia [DAD] and MMSE scores) between the bapi /bapi and placebo/bapi groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E ) occurred in 22 (11.3%) patients . The most common TEAEs (>20% patients ) were fall, agitation and urinary tract infection with similar incidences between bapi /bapi and placebo/bapi groups. CONCLUSION: No significant difference was seen in cognitive and functional decline between early and delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed to death events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities: Chemical
Disease
Gene
Species
Keywords:
AD assessment scale; Alzheimer's disease; MRI; bapineuzumab; brain amyloid-related imaging abnormality; disabilityzzm321990assessment for dementia.
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Year: 2018
PMID： 30129411 DOI： 10.2174/1567205015666180821114813
Source DB: PubMed Journal: Curr Alzheimer Res ISSN： 1567-2050 Impact factor: 3.498