AAB-003(AAB-003) - 药物靶点：APP_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

靶点

APP

作用机制

APP抑制剂(β-淀粉状蛋白A4抑制剂)

治疗领域

神经系统疾病

在研适应症-

非在研适应症

阿尔茨海默症

原研机构

Pfizer Inc.

在研机构-

非在研机构

Janssen Alzheimer Immunotherapy Research & Development LLC

Elan Corp. Plc

Pfizer Inc.

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 AAB-003 相关的临床试验

NCT01369225 / Completed临床1期

A Multicenter, Open-label Extension, Multiple Dose, Parallel Group Study To Investigate The Long-term Safety And Tolerability Of Aab-003 (Pf-05236812) Administered Intravenously In Subjects With Mild To Moderate Alzheimer's Disease Previously Treated With Aab-003 Or Placebo In Protocol B2601001

This is a study to evaluate the safety and tolerability of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients who complete study B2601001 may participate in this trial and receive AAB-003 (PF-05236812). Each patient's participation will last approximately 52 weeks.

开始日期2011-07-01

申办/合作机构

Pfizer Inc.

[+1]

NCT01193608 / Completed临床1期

A Phase 1, Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptive, Multiple Ascending Dose Study Of The Safety, Tolerability And Pharmacokinetics Of Aab-003 (Pf-05236812) In Subjects With Mild To Moderate Alzheimer's Disease

This is a study to evaluate the safety of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients will receive either AAB-003 (PF-05236812) or placebo. Each patient's participation will last approximately 41 weeks.

开始日期2010-09-01

申办/合作机构

Pfizer Inc.

[+1]

100 项与 AAB-003 相关的临床结果

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100 项与 AAB-003 相关的转化医学

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100 项与 AAB-003 相关的专利（医药）

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2

项与 AAB-003 相关的文献（医药）

2016-12-01·Alzheimer's Research & Therapy2区 · 医学

First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer’s disease

2区 · 医学

ArticleOA

作者: Duvvuri, Sridhar ; Lu, Ming ; Ness, Seth ; Li, David Jianjun ; Atassi, Nazem ; Kupiec, James W ; Brashear, H Robert ; Delnomdedieu, Marielle ; Liu, Enchi

AbstractBackgroundIn the First-In-Human (FIH), 39-week, randomized, adaptive design study, safety, tolerability, pharmacokinetics and biomarkers were measured in patients with mild-to-moderate Alzheimer’s disease (AD) after infusion of a humanized monoclonal antibody to amyloid β, AAB-003 (NCT01193608; registered 19 August 2010). AAB-003 was developed by modifying bapineuzumab to reduce Fc-receptor-mediated effector function as a strategy to reduce the removal of amyloid from vessel walls associated with amyloid-related imaging abnormalities with edema/effusions (ARIA-E) without diminishing overall amyloid clearance.MethodsEighty-eight patients with AD received up to three infusions of AAB-003 (or placebo) 13 weeks apart at doses of 0.5, 1, 2, 4 or 8 mg/kg in the FIH trial. Dose escalation was based on safety data reviews using a Bayesian escalation algorithm. Subjects who completed the FIH study were permitted to enter a 1-year open-label extension trial with four additional intravenous infusions of AAB-003 (NCT01369225; registered 10 May 2011).ResultsDose-dependent increases in plasma amyloid β and AAB-003 were observed. No significant changes in cerebral spinal fluid biomarkers were observed. Pharmacokinetics elimination half-life (21–28 days) clearance and volume of distribution values were consistent across dose groups indicating linearity. ARIA-E was the most notable safety finding detected by magnetic resonance imaging (MRI) at 8 mg/kg in two patients. Three cases of microhemorrhage were observed. No new safety findings or MRI abnormalities were observed for the 52 subjects who received AAB-003 in the extension trial.ConclusionBased on integrated review of laboratory, electrocardiogram, adverse events, and MRI, AAB-003 was safe and well tolerated up to 8 mg/kg for up to 91 weeks (FIH and extension trials) in patients with mild to moderate AD. Asymptomatic and resolvable ARIA-E was observed after the first or second infusion of AAB-003, similar to bapineuzumab. The AAB-003 dose at which ARIA-E was observed was higher compared to bapineuzumab, supporting the hypothesis that reducing Fc-receptor effector function may reduce the ARIA associated with monoclonal antibodies targeting cerebral amyloid.

2014-03-01·Acta Crystallographica Section F Structural Biology Communications4区 · 生物学

Crystallization and preliminary X-ray diffraction analysis of the Fab portion of the Alzheimer's disease immunotherapy candidate bapineuzumab complexed with amyloid-β

4区 · 生物学

Article

作者: Luke A. Miles ; Michael W. Parker ; David B. Ascher ; Gabriela A. N. Crespi

Bapineuzumab (AAB-001) and its derivative (AAB-003) are humanized versions of the anti-Aβ murine antibody 3D6 and are immunotherapy candidates in Alzheimer's disease. The common Fab fragment of these immunotherapies has been expressed, purified and crystallized in complex with β-amyloid peptides (residues 1-8 and 1-28). Diffraction data at high resolution were acquired from crystals of Fab-Aβ8 (2.0 Å) and Fab-Aβ28 (2.2 Å) complexes at the Australian Synchrotron. Both crystal forms belonged to the primitive orthorhombic space group P21221.

100 项与 AAB-003 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床1期	-	Elan Corp. Plc	-
阿尔茨海默症	临床1期	-	Elan Corp. Plc	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01369225 (CTgov)	临床1期	阿尔茨海默症	52	AAB-003 (AAB-003 0.5 mg/kg)	艱蓋廠鏇鏇繭製觸築構(鏇網艱襯襯廠鏇遞齋糧) = 鬱製積醖鏇鏇衊觸繭夢艱範顧餘壓製積積醖壓 (鬱選淵壓醖積鏇構選醖, 範願積夢鑰廠鏇遞淵廠 ~ 餘醖衊夢選積觸廠淵衊) 更多	-	2017-03-10
NCT01369225 (CTgov)	临床1期	阿尔茨海默症	52	AAB-003 (AAB-003 1 mg/kg)	艱蓋廠鏇鏇繭製觸築構(鏇網艱襯襯廠鏇遞齋糧) = 繭製憲艱鬱廠膚鏇鑰糧艱範顧餘壓製積積醖壓 (鬱選淵壓醖積鏇構選醖, 窪艱願選簾壓蓋選齋選 ~ 遞廠壓網壓餘艱廠積構) 更多	-	2017-03-10
NCT01193608 (CTgov)	临床1期	阿尔茨海默症	88	Placebo	積蓋繭衊壓糧窪構鏇餘(築獵鹹積襯蓋糧鏇網鹹) = 製艱顧夢簾糧淵餘範壓淵襯鹽壓願鹽壓糧襯齋 (顧鹽選鑰築衊膚廠築蓋, 蓋鑰夢艱夢鹽夢簾遞鑰 ~ 遞糧築衊鹹廠製顧艱鬱) 更多	-	2017-02-23