Actoxumab/Bezlotoxumab(Actoxumab/Bezlotoxumab) - 药物靶点：toxA x toxB_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Bezlotoxumab/actoxumab

+ [8]

靶点

toxA x toxB

作用机制

toxA抑制剂(艰难梭菌毒素A抑制剂)、toxB抑制剂(艰难梭菌毒素B抑制剂)

治疗领域

感染

在研适应症-

非在研适应症

艰难梭菌感染

原研机构

Merck & Co., Inc.

在研机构-

非在研机构

Merck Sharp & Dohme LLC

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 9173798L

当前序列信息引自: *****

Sequence Code 319373281H

当前序列信息引自: *****

Sequence Code 13006926H

当前序列信息引自: *****

Sequence Code 9173761L

当前序列信息引自: *****

关联

5

项与 Actoxumab/Bezlotoxumab 相关的临床试验

EUCTR2011-004994-94-CZ / Not yet recruitingN/A

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to C. difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to C. difficile toxin A and B) in Patients Receiving Antibiotic Therapy for C. difficile Infection (MODIFY II) - MODIFY II

开始日期2012-03-06

申办/合作机构

Merck & Co., Inc.

NCT01513239 / Completed临床3期

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of a Single Infusion of MK-6072 (Human Monoclonal Antibody to Clostridium Difficile Toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium Difficile Toxin A and B) in Patients Receiving Antibiotic Therapy for Clostridium Difficile Infection (MODIFY II)

MK-3415A is the combination of monoclonal antibodies to Clostridium (C.) difficile toxin A (MK-3415) and toxin B (MK-6072). This study will investigate whether: 1) treatment with MK-6072 or MK-3415A in addition to standard of care (SOC) antibiotic therapy will decrease Clostridium Difficile Infection (CDI) recurrence compared with placebo; and 2) MK-6072 and MK-3415A will be generally well tolerated in participants receiving SOC therapy for CDI compared with placebo.

开始日期2012-02-01

申办/合作机构

Merck Sharp & Dohme LLC

EUCTR2011-004590-90-ES / Not yet recruiting临床3期

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of the Efficacy, Safety, and Tolerability of a Single Infusion of MK-3415 (Human Monoclonal Antibody to Clostridium difficile toxin A), MK-6072 (Human Monoclonal Antibody to Clostridium difficile toxin B), and MK-3415A (Human Monoclonal Antibodies to Clostridium difficile toxin A and toxin B) in Patients Receiving Antibiotic Therapy for Clostridium difficile Infection(MODIFY I) - MODIFY I

开始日期2012-01-27

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 Actoxumab/Bezlotoxumab 相关的临床结果

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100 项与 Actoxumab/Bezlotoxumab 相关的转化医学

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100 项与 Actoxumab/Bezlotoxumab 相关的专利（医药）

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23

项与 Actoxumab/Bezlotoxumab 相关的文献（医药）

2024-07-23·Journal of Virology

Mouse and human immune responses share neutralization epitopes of HAstV-VA1

Article

作者: Arias, Carlos F ; Alpuche-Aranda, Celia M ; DuBois, Rebecca M ; López, Susana ; Gaspar-Castillo, Carlos ; Ramírez-Bello, Inci ; Riaño-Umbarila, Lidia ; Ghosh, Anisa ; Espinosa, Rafaela ; Green, Kassidy ; López, Tomás ; Aguilera-Flores, Catalina

ABSTRACTAstroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in human astroviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient’s immunotherapy. In agreement with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, suggesting that both mouse and human antibody responses target shared neutralization epitopes. The isolated Nt-MAbs reported in this work will help to characterize the functional domains of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.IMPORTANCEHuman astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. In this work high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1 were isolated and characterized. The proposed binding sites for these antibodies and for neutralizing antibodies against classical HAstVs suggest that there are at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will help to define the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

2020-01-01·Animal Science Journal3区 · 农林科学

Administration of L. salivarius expressing 3D8 scFv as a feed additive improved the growth performance, immune homeostasis, and gut microbiota of chickens

3区 · 农林科学

Article

作者: Oh, Keon Bong ; Byun, Sung June ; Lee, Sukchan ; Lee, Hae Sun ; Lee, Hwi Cheul ; Sureshkumar, Shanmugam ; Yang, Hyeon ; Kim, Dongjun ; Jung, Sun Keun ; Jo, Yong Jin

AbstractProbiotics have been defined as live microorganisms that are administered in an appropriate amount to provide health benefits to the host animal. In this study, we investigated the effect of L. salivarius DJ‐sa‐01 secreting the 3D8 single‐chain variable fragment (3D8 scFv) on the growth performance, cytokine secretion, and intestinal microbial flora of chickens. The experiment was divided into the control group and L. salivarius expressing 3D8 scFv experimental group. Chicken was fed 109 colony‐forming units (CFUs) of wild‐type (WT) L. salivarius or 3D8 scFv‐secreting L. salivarius daily for 35 days. The administration of L. salivarius expressing 3D8 scFv significantly improved the body weight of chickens compared with the administration of WT L. salivarius. A 16S ribosomal RNA metagenomic analysis showed that Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the dominant phyla in both experimental groups. At the genus level, Lactobacillus was more abundant (22.82%) in the L. salivarius/3D8 group compared with the WT L. salivarius group. The serum levels of cytokines, such as IL‐8, TNF‐α, IL‐1β, IFN‐γ, IL‐4, and IGF1, were significantly reduced in the L. salivarius/3D8‐treated chickens. In summary, our results suggest that L. salivarius expressing 3D8 scFv could be considered a feed additive for improving the growth performance, immune function, and disease resistance of poultry.

2019-12-01·Acta Veterinaria Hungarica4区 · 农林科学

Avian influenza virus transmission is suppressed in chickens fed Lactobacillus paracasei expressing the 3D8 single-chain variable fragment protein

4区 · 农林科学

Article

作者: Park, Mi-Ryung ; Byun, Sung June ; Choi, Hoonsung ; Kim, Kyung-Woon ; Kim, Jeom Sun ; Jeon, Ik-Soo ; Lee, Sukchan ; Lee, Sang In ; Sureshkumar, Shanmugam ; Jeon, Mi-Hyang

The 3D8 single-chain variable fragment (scFv) is a mini-antibody sequence with independent nuclease activity that shows antiviral effects against all types of viruses in chickens and mice. In this study, chickens were treated daily with an oral dose of 109 CFU Lactobacillus paracasei (L. paracasei) expressing either a secreted or anchored 3D8 scFv for three weeks. After L. paracasei administration, the chickens were challenged with avian influenza virus (AIV). From each experimental group, three chickens were directly infected with 100 µL of 107.5 EID50/mL H9N2 AIV and seven chickens were indirectly challenged through contact transmission. oropharyngeal and cloacal swab samples were collected at 3, 5, 7, and 9 days post-inoculation (dpi) from AIV-challenged chickens, AIV Shedding titres were measured by quantitative real-time PCR. Contact transmission in the chickens that were fed 3D8 scFv-secreting L. paracasei showed a significant reduction in viral shedding when compared with other groups. These results suggest that L. paracasei secreting 3D8 provides a basis for the development of ingestible antiviral probiotics with activity against AIV.

100 项与 Actoxumab/Bezlotoxumab 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
艰难梭菌感染	临床3期	-	Merck Sharp & Dohme LLC	2011-10-10

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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


NCT00350298 (CTgov)	临床2期	艰难梭菌结肠炎	200	GS-CDA1/MDX-1388 (GS-CDA1/MDX-1388)	淵製襯繭範壓選鹹憲膚(簾鏇範積願糧築鹹齋衊) = 築積遞簾簾襯餘壓夢蓋積壓夢鹹鹽積製積選製 (簾構鏇構簾繭選獵遞襯, 膚淵鬱餘淵鏇餘構艱觸 ~ 醖壓蓋鑰獵選夢網淵糧) 更多	-	2021-02-09
				normal saline (Placebo)	淵製襯繭範壓選鹹憲膚(簾鏇範積願糧築鹹齋衊) = 選顧憲願齋鹽網鏇夢獵積壓夢鹹鹽積製積選製 (簾構鏇構簾繭選獵遞襯, 夢遞壓遞鹽積壓繭鹹膚 ~ 憲齋繭齋範選構鬱積鹽) 更多
MODIFY I and MODIFY II (Pubmed \| Br Dent J)	临床3期	艰难梭菌感染	2,655	Bezlotoxumab	製醖觸鬱窪鹽獵鏇艱膚(夢齋廠窪顧築鬱鏇鹹遞) = 衊觸獵繭夢觸齋簾鏇鬱鹹艱蓋觸範艱鑰廠醖襯 (醖艱築糧願積齋範淵襯 ) 更多	积极	2017-01-26
				Actoxumab plus Bezlotoxumab	製醖觸鬱窪鹽獵鏇艱膚(夢齋廠窪顧築鬱鏇鹹遞) = 蓋餘鬱糧醖積顧網繭獵鹹艱蓋觸範艱鑰廠醖襯 (醖艱築糧願積齋範淵襯 ) 更多
NCT01513239 (MODIFY II \| 3415A-002, CTgov)	临床3期	艰难梭菌感染	1,203	SOC+MK-3415A (MK-3415A + SOC)	鑰鏇餘壓鏇製願積築觸(膚膚鹹築積鑰積夢選選) = 蓋積築襯顧艱醖觸鹹齋壓遞範糧鏇鑰廠憲鏇選 (鏇壓蓋範鏇憲壓廠夢觸, 積鏇廠襯憲醖糧範鹹襯 ~ 積製鹹構鏇鬱蓋願醖繭) 更多	-	2016-12-15
				SOC+MK-6072 (MK-6072 + SOC)	鑰鏇餘壓鏇製願積築觸(膚膚鹹築積鑰積夢選選) = 廠餘憲觸願簾廠衊網蓋壓遞範糧鏇鑰廠憲鏇選 (鏇壓蓋範鏇憲壓廠夢觸, 鬱醖鏇壓鬱範鑰憲壓窪 ~ 蓋淵鑰簾選衊構簾鬱壓) 更多
NCT01241552 (MODIFY I \| 3415A-001, CTgov)	临床3期	艰难梭菌感染	1,452	SOC+MK-3415 (MK-3415 + SOC)	遞齋憲蓋窪夢選鏇膚積(夢製膚簾鹽餘遞糧糧壓) = 糧繭齋積蓋繭積醖築蓋觸醖積構繭觸鑰鹽齋築 (獵範壓鹹範構觸鏇簾膚, 築簾築憲鏇蓋壓壓鏇醖 ~ 構顧願積齋製憲醖築鑰) 更多	-	2016-12-15
				SOC+MK-6072 (MK-6072 + SOC)	遞齋憲蓋窪夢選鏇膚積(夢製膚簾鹽餘遞糧糧壓) = 衊範夢鑰顧鏇簾遞顧壓觸醖積構繭觸鑰鹽齋築 (獵範壓鹹範構觸鏇簾膚, 衊遞製餘鑰製顧壓繭鏇 ~ 膚顧齋選鬱製窪襯壓鏇) 更多