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A randomized, doubl...
A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-A beta protofibril antibody
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- Swanson, Chad J. (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Zhang, Yong (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Dhadda, Shobha (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Wang, Jinping (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Kaplow, June (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Lai, Robert Y. K. (författare)
- Eisai Ltd, Hatfield, Herts, England.
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- Lannfelt, Lars (författare)
- Uppsala universitet,Geriatrik,BioArctic, Warfvinges Vag 35, SE-11251 Stockholm, Sweden.
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- Bradley, Heather (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Rabe, Martin (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Koyama, Akihiko (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Reyderman, Larisa (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Berry, Donald A. (författare)
- Berry Consultants LLC, Austin, TX USA.
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- Berry, Scott (författare)
- Berry Consultants LLC, Austin, TX USA.
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- Gordon, Robert (författare)
- Eisai Ltd, Hatfield, Herts, England.
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- Kramer, Lynn D. (författare)
- Eisai Inc, Woodcliff Lake, NJ USA.
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- Cummings, Jeffrey L. (författare)
- Univ Nevada Las Vegas, Grundy Ctr Transformat Neurosci, Sch Integrated Hlth Sci, Dept Brain Hlth, Las Vegas, NV USA.
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Eisai Inc, Woodcliff Lake, NJ USA Eisai Ltd, Hatfield, Herts, England. (creator_code:org_t)
- 2021-04-17
- 2021
- Engelska.
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 13
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://alzres.biome...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (A beta), 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: BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer's disease is underway.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Alzheimer's disease
- Amyloid
- Lecanemab
- BAN2401
- Clinical trial
- Biomarker
- ADCOMS
- Amyloid PET
- Neurofilament light
- Neurogranin
- p-tau
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Swanson, Chad J.
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Zhang, Yong
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Dhadda, Shobha
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Wang, Jinping
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Kaplow, June
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Lai, Robert Y. K ...
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visa fler...
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Lannfelt, Lars
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Bradley, Heather
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Rabe, Martin
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Koyama, Akihiko
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Reyderman, Laris ...
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Berry, Donald A.
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Berry, Scott
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Gordon, Robert
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Kramer, Lynn D.
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Cummings, Jeffre ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Alzheimer's Rese ...
- Av lärosätet
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Uppsala universitet