A Phase 2b/3, Multi-Center, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Pagibaximab Injection in Very Low Birth Weight (VLBW) Neonates for the Prevention of Staphylococcal Sepsis

开始日期2009-12-22

申办/合作机构

Biosynexus, Inc.

NCT00646399 / Completed临床2/3期

Evaluate the safety, PK and efficacy comparing Pagibaximab Injection to placebo in preventing staphylococcal sepsis in very low birth weight infants. 1550 infants will be enrolled prior to 48 hours of life and will be randomized 1:1 to receive active drug or placebo on study days 0, 1, 2, 9, 16, and 23.

开始日期2009-03-01

申办/合作机构

Biosynexus, Inc.

NCT00631800 / Completed临床2期

Phase II Randomized, Double Blind, Placebo Controlled, Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity Study in VLBW Neonates of BSYX-A110, for the Prevention of Staphylococcal Infection

The purpose of this study is to evaluate the safety (including tolerability), pharmacokinetics, pharmacodynamics and clinical activity of BSYX-A110 administered in a 3-dose regimen on Study Days 0, 7, and 14.

开始日期2003-05-01

申办/合作机构

Biosynexus, Inc.

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100 项与帕昔单抗相关的临床结果

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100 项与帕昔单抗相关的转化医学

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100 项与帕昔单抗相关的专利（医药）

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项与帕昔单抗相关的文献（医药）

2020-04-01·JOURNAL OF CLINICAL PHARMACOLOGY

Integration of Ontogeny Into a Physiologically Based Pharmacokinetic Model for Monoclonal Antibodies in Premature Infants.

Article

作者: Edginton, Andrea N ; Malik, Paul R V

An understanding of pediatric pharmacokinetics (PK) is essential for first-in-pediatric dose selection and clinical trial design. At present, there is no reliable way to scale the PK of monoclonal antibodies and immunoglobulin G drug products from adults to young children or to premature infants-a vulnerable population with a rapidly growing drug development pipeline. In this work, pediatric physiologically based PK models are constructed in PK-Sim and Mobi to explore the PK of pagibaximab, palivizumab, MEDI8897, and intravenous immunoglobulin in preterm infants. In addition to considering ontogeny in pediatric organ volumes, organ composition, blood flow rates, and hematocrit, advanced ontogeny is applied for 3 key parameters: capillary surface area, hematopoietic cell concentration, and lymph flow rate. The role and importance of each parameter for determining pediatric clearance (CL) and volume of distribution at steady state (V_SS ) are quantitatively assessed with a local sensitivity analysis. In addition, the uncertainty around parameters with limited information in pediatrics is addressed (eg, free neonatal Fc receptor concentration). The full ontogeny parameterization yields pediatric PK predictions that are within 1.5-fold prediction error >90% of the time for preterm infants, with an absolute average fold error of 1.05. This result suggests that many of the key factors related to ontogeny are appropriately addressed. Overall, this study makes a first step toward developing a platform pediatric physiologically based PK model for monoclonal antibodies and immunoglobulin G drug products by solidifying existing parameterizations, integrating new concepts, and drawing attention to unmet needs for physiologic knowledge in children.

2019-06-01·Virologica Sinica2区 · 医学

Localization Analysis of Heterophilic Antigen Epitopes of H1N1 Influenza Virus Hemagglutinin

2区 · 医学

Article

作者: Zhang, Jun-Jun ; Li, Hui-Jin ; Sun, Li-Jun ; Guo, Chun-Yan ; Xie, Xin ; Li, Yan ; Zhang, Hai-Xiang ; Hu, Jun ; Liang, Dao-Yan ; Feng, Qing ; Feng, Yang-Meng

Previous studies have indicated that two monoclonal antibodies (mAbs; A1-10 and H1-84) of the hemagglutinin (HA) antigen on the H1N1 influenza virus cross-react with human brain tissue. It has been proposed that there are heterophilic epitopes between the HA protein and human brain tissue (Guo et al. in Immunobiology 220:941-946, 2015). However, characterisation of the two mAbs recognising the heterophilic epitope on HA has not yet been performed. In the present study, the common antigens of influenza virus HA were confirmed using indirect enzyme-linked immunosorbent assays and analysed with DNAMAN software. The epitopes were localized to nine peptides in the influenza virus HA sequence and the distribution of the peptides in the three-dimensional structure of HA was determined using PyMOL software. Key amino acids and variable sequences of the antibodies were identified using abYsis software. The results demonstrated that there were a number of common antigens among the five influenza viruses studied that were recognised by the mAbs. One of the peptides, P2 (LVLWGIHHP_191-199), bound both of the mAbs and was located in the head region of HA. The key amino acids of this epitope and the variable regions in the heavy and light chain sequences of the mAbs that recognised the epitope are described. A heterophilic epitope on H1N1 influenza virus HA was also introduced. The existence of this epitope provides a novel perspective for the occurrence of nervous system diseases that could be caused by influenza virus infection, which might aid in influenza prevention and control.

2016-09-20·Biochemistry3区 · 生物学

Inhibition of Inosine-5′-monophosphate Dehydrogenase from Bacillus anthracis: Mechanism Revealed by Pre-Steady-State Kinetics

3区 · 生物学

Article

作者: Wei, Yang ; Hedstrom, Lizbeth ; Yu, Runhan ; Modi, Gyan ; Kuzmič, Petr

Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the conversion of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP). The enzyme is an emerging target for antimicrobial therapy. The small molecule inhibitor A110 has been identified as a potent and selective inhibitor of IMPDHs from a variety of pathogenic microorganisms. A recent X-ray crystallographic study reported that the inhibitor binds to the NAD(+) cofactor site and forms a ternary complex with IMP. Here we report a pre-steady-state stopped-flow kinetic investigation of IMPDH from Bacillus anthracis designed to assess the kinetic significance of the crystallographic results. Stopped-flow kinetic experiments defined nine microscopic rate constants and two equilibrium constants that characterize both the catalytic cycle and details of the inhibition mechanism. In combination with steady-state initial rate studies, the results show that the inhibitor binds with high affinity (Kd ≈ 50 nM) predominantly to the covalent intermediate on the reaction pathway. Only a weak binding interaction (Kd ≈ 1 μM) is observed between the inhibitor and E·IMP. Thus, the E·IMP·A110 ternary complex, observed by X-ray crystallography, is largely kinetically irrelevant.

项与帕昔单抗相关的新闻（医药）

2024-05-25

·信达生物

世界甲状腺日 | 了解甲状腺眼病，守护“心灵之窗”

每年的5月25日是 “世界甲状腺日”， 5月20日-26日是第十六届“国际甲状腺知识宣传周"，今年宣传周的主题为“甲状腺疾病也是一种慢性病！”今天，小编和大家聊一聊一种严重影生活质量的甲状腺相关疾病——甲状腺眼病（Thyroid Eye Disease, TED）。甲状腺眼病，又称格雷夫斯眼病（Graves’ ophthalmopathy, GO），这个听起来有点神秘的疾病，其实是继发于甲状腺疾病的眼部自身免疫性疾病，是成年人中最常见的眼眶病。TED会引起眼部不适、眼球突出、眼部红肿、视物重影等，不仅严重影响外观，还会影响视功能，甚至导致失明。TED除了给患者日常生活和工作带来影响，还可能打击患者的自尊心、自信心，严重危害身心健康。偷走了美丽，带来了“哀愁”。更让人头疼的是，针对TED，中国目前可用的治疗药物非常有限，60年无有效新药上市，且已有治疗的效果往往不尽如人意。目前仅极少数发达国家有相关靶向药获批上市，而且高昂的治疗费用让绝大多数患者望而却步。我们呼吁，大家重视TED的早期诊断和治疗，同时我们也期待有更多治疗TED的创新药物尽早上市，守护我们的“心灵之窗”。甲状腺眼病（TED）是什么？TED是一种累及眼部组织的自身免疫性疾病，通常伴发于毒性弥漫性甲状腺肿（Graves病，GD），是成人中最常见的眼眶相关疾病。TED可见于大约25~50%的GD患者，也可见于其他甲状腺疾病，甚至甲状腺功能正常者1。甲状腺眼病的发病现状？TED的年发病率预估为16/100,000人（女性）和2.9/100,000人（男性）2，患病率为0.1-0.3%3 。按照疾病严重程度，可分为轻度、中重度和极重度。虽然TED更常发生于女性，但重度病例更常发生于男性。TED最常见于30~50岁的患者，严重TED病例更常发生于50岁以上的患者4。目前，TED的发病机制尚不完全清楚，但多项研究表明，存在于肌纤维、眼眶纤维结缔组织间隙中的眼眶成纤维细胞（Orbital Fibroblasts, OFs）是导致TED眼眶软组织增生的关键因素5。甲状腺眼病的常见症状？TED的自然病程分为活动期和非活动期6。最常见的症状是眼干、眼部异物感、畏光、流泪、视物重影和眼后压迫感，而典型的体征包括眼球突出、上眼睑退缩、眶周组织和球结膜充血、水肿、眼球运动受限等。TED通常为轻度到中重度，约3~5%的TED患者会发展至极重度，表现为威胁视力的角膜溃疡或压迫性视神经病变等7。除了可能影响外观和视功能，TED对患者的社交功能和生活质量产生极其严重的影响。如果生活中遇到类似症状请尽早去医院就医治疗。甲状腺眼病的常见治疗手段？目前，中重度活动性TED的一线治疗方案为糖皮质激素静脉冲击治疗，存在突眼改善不理想、复发率高以及激素相关的全身副作用等问题，仍存在较大的未满足的临床需求。二线治疗包括再次激素冲击或联合眼眶放疗或其他免疫调节剂。此外，替妥尤单抗（Teprotumumab，IGF-1R抗体）、托珠单抗（TociIizumab，IL-6R抗体）和利妥昔单抗（Rituximab，CD20抗体）等生物制剂也被欧洲Graves眼病专家组指南（EUGOGO 指南）8、中国甲状腺眼病临床诊断和治疗指南（2022年）9、美国甲状腺学会和欧洲甲状腺学会的甲状腺眼病共识10推荐为中重度活动性TED的二线治疗方案。尤其对于合并显著突眼的TED，美国甲状腺学会和欧洲甲状腺学会的甲状腺眼病共识推荐替妥尤单抗可作为首选，但是中国尚无同类靶向药物获批上市。对于非活动期TED，若眼球突出、复视/斜视或眼睑畸形影响患者外观和视功能，需进行眼部相关矫正手术（包括眼眶减压手术、斜视矫正手术及眼睑矫正手术），但难以完全恢复到患病前状态。TED手术治疗复杂，手术风险高且创伤大，可及性较低。替妥尤单抗的出现则有望打破非活动期TED仅能手术治疗的困境，它可以显著缓解非活动期TED患者的眼球突出，并改善患者的视功能。因此，国内开发有效、安全且可及的靶向IGF-1R药物对于中国TED患者具有重要的临床及社会价值。替妥尤单抗（IGF-1R抗体）的作用机制？IGF-1R是一种跨膜酪氨酸激酶受体，在发育、代谢及免疫调节中发挥作用，并在TED患者的OFs、B细胞、T细胞中过表达。替妥尤单抗（IGF-1R抗体）可阻断IGF-1等相关配体或激动型抗体介导的IGF-1R信号通路激活，减少下游炎症因子的表达，从而抑制OFs活化导致的透明质酸和其他糖胺聚糖合成，减轻炎症反应；抑制OFs分化为脂肪细胞或肌成纤维细胞，进而减轻TED患者的疾病活动度，改善突眼、复视、眼部充血水肿等症状和体征。信达生物一直致力于解决尚未满足的临床需求，5月21日，信达生物替妥尤单抗（IGF-1R抗体）新药上市申请获国家药品监督管理局正式受理，用于治疗甲状腺眼病。替妥尤单抗是中国首个申报上市的IGF-1R抗体，作为具有创新作用机制的生物药，有望填补国内TED治疗领域60年来无新药可用的空白，满足国内TED治疗的显著临床需求，为中国TED患者带来有效、安全、可及的治疗手段。参考文献1.Dolman P J. Evaluating Graves’ orbitopathy. Best Pract Res Clin Endocrinol Metab.2012;26(3):229-248.2.Li Z, Cestari D M, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018;29(6):528-534.3.Bartley G. The epidemiological characteristics and clinical course of ophthalmology associated with autoimmune thyroid disease in Olmsted Country, Minnesota. Trans Am Ophthalmol Soc 1994;92:477-588.4.Bahn R S. Graves’ ophthalmopathy. N Engl J Med. 2010;362(8):726-738.5.Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185(4):G43-G67.6.中华医学会眼科学分会眼整形眼眶病学组, 中华医学会内分泌学分会甲状腺学组. 中国甲状腺相关眼病诊断和治疗指南（2022年）.中华眼科杂志. 2022;58(9).7.Burch HB, et al. Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022;11(6):e220189.8.Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves' ophthalmopathy: epidemiology and natural history. Intern Med. 2014;53(5):353-60.9.Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7, 2011, from Medscape Reference: http://emedicine.medscape.com/article/1218444-overview#a110.Ali F, Chorsiya A, Anjum V, Ali A. Teprotumumab (TEPEZZA): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment. Int Ophthalmol. 2021;41(4):1549-1561.

临床研究临床结果

100 项与帕昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08960	帕昔单抗	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
脓毒症	临床3期	美国	Biosynexus, Inc.	2009-03-01
葡萄球菌感染	临床3期	美国	Biosynexus, Inc.	2009-03-01
新生儿败血症	临床2期	美国	Biosynexus, Inc.	2001-11-01

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适应症

分期

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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


NCT00646399 (CTgov)	临床2/3期	葡萄球菌感染	1,579	Placebo	淵膚廠製遞鏇觸繭願憲(蓋鏇簾醖醖齋憲網憲廠) = 鹹鏇窪醖餘蓋遞鹹衊醖構艱蓋鬱鏇觸鏇觸製餘 (選膚夢積簾艱窪築艱窪, 選齋鹹範膚繭廠醖艱鏇 ~ 廠繭製醖鏇範膚遞製獵) 更多	-	2011-10-24