Academic Journal
A Randomized, Double-Blind, Phase 2b Proof-of-Concept Clinical Trial in Early Alzheimer’s Disease With Lecanemab, an Anti-aβ Protofibril Antibody
| العنوان: | A Randomized, Double-Blind, Phase 2b Proof-of-Concept Clinical Trial in Early Alzheimer’s Disease With Lecanemab, an Anti-aβ Protofibril Antibody |
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| المؤلفون: | Swanson, Chad J., Zhang, Yong, Dhadda, Shobha, Wang, Jinping, Kaplow, June, Lai, Robert Y.K., Lannfelt, Lars, Bradley, Heather, Rabe, Martin, Koyama, Akihiko, Reyderman, Larisa, Berry, Donald A., Berry, Scott, Gordon, Robert, Kramer, Lynn D., Cummings, Jeffrey L. |
| المصدر: | School of Medicine Faculty Publications |
| بيانات النشر: | Digital Scholarship@UNLV |
| سنة النشر: | 2021 |
| المجموعة: | University of Nevada, Las Vegas: Digital Scholarship@UNLV |
| مصطلحات موضوعية: | ADCOMS, Alzheimer’s disease, Amyloid, Amyloid PET, BAN2401, Biomarker, Clinical trial, Lecanemab, Neurofilament light, Neurogranin, p-tau, Cognitive Neuroscience |
| الوصف: | Background: Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods: BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results: A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions: ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://digitalscholarship.unlv.edu/som_fac_articles/626; https://digitalscholarship.unlv.edu/cgi/viewcontent.cgi?article=1625&context=som_fac_articles |
| الاتاحة: | https://digitalscholarship.unlv.edu/som_fac_articles/626 https://digitalscholarship.unlv.edu/cgi/viewcontent.cgi?article=1625&context=som_fac_articles |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.D6B8388F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |