A Phase 3, Multicenter, Randomized, Partially Blinded, Palivizumab- Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MK-1654 in Infants and Children at Increased Risk for Severe RSV Disease

This study aims to evaluate the safety and tolerability of clesrovimab compared to palivizumab as assessed by the proportion of participants experiencing adverse events (AEs).

开始日期2021-11-30

申办/合作机构

Merck Sharp & Dohme Corp.

CTR20211903 / Completed临床1期

一项在中国健康受试者中评价MK-1654安全性和耐受性的开放性、单剂临床研究

根据受试者中出现不良事件（AE）的比例，评估MK-1654的安全性和耐受性

开始日期2021-10-08

申办/合作机构

默沙东研发（中国）有限公司

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100 项与 Clesrovimab 相关的临床结果

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100 项与 Clesrovimab 相关的转化医学

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100 项与 Clesrovimab 相关的专利（医药）

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项与 Clesrovimab 相关的文献（医药）

2024-09-01·REVIEWS IN MEDICAL VIROLOGY

Systematic Review of the Efficacy and Safety of RSV‐Specific Monoclonal Antibodies and Antivirals in Development

Review

作者: Hurley, Siobhan ; Rawlinson, William ; Bartlett, Adam W. ; Walker, Gregory J. ; Sevendal, Andrea T. K.

ABSTRACT:

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely‐publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR—searched Nov 29th, 2023) to identify studies on all RSV‐specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab‐YTE, nirsevimab, ALX‐0171, suptavumab, clesrovimab) and 12 AV therapies (ALN‐RSV01, RSV604, presatovir, MDT‐637, lumicitabine, IFN‐α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP‐938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV‐specific AV availability is less advanced, although EDP‐938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development.

Trial Registration:

PROSPERO registration: CRD42022376633

2024-01-01·Asian Journal of Transfusion Science

Identification of rare anti-f alloantibody in a tertiary care center in India

Article

作者: Tewari, Ashish ; Tiwari, Deepak ; Bhardwaj, Gunjan ; Vishwakarma, Sanjay

Abstract::

A 68-year-old male known follow-up patient of nonalcoholic steatohepatitis and carcinoma stomach was admitted to hospital for further management. The patient was planned for radical gastrectomy and required two units of packed red blood cell (PRBC), due to low hemoglobin of 6.6 g/dl. The patient blood grouping and antibody screening (ABS) were done. Patient ABS was positive. On antibody identification, using eleven-cell identification panel, resolve Panel A (Ortho Clinical Diagnostics, Johnson and Johnson, USA), “anti-f” alloantibody was identified in the patient sample. Select cells, from another resolve panel were used to rule out remaining antibodies. Anti-f antibody is produced due to the exposure of “f antigen.” Anti-f antibody can cause hemolytic disease of fetus and new-born and possible hemolytic transfusion reactions. At our center, we successfully transfused two units of anti-human globulin compatible and “c-negative” units, to the patient without any adverse reactions. Thus, the patient having anti-f antibody can be managed by transfusing “c-negative” or “e-negative” PRBC units or units lacking both the “c” and “e” antigens.

2023-12-01·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Quantification of clesrovimab, an investigational, half-life extended, anti-respiratory syncytial virus protein F human monoclonal antibody in the nasal epithelial lining fluid of healthy adults

Article

作者: Cao, Yu ; Caro, Luzelena ; Maas, Brian M ; Aliprantis, Antonios O ; Tang, Aimin ; Phuah, Jia Yao ; Swanson, Michael D ; Li, Hankun ; Vora, Kalpit A ; Catchpole, Andrew P ; Railkar, Radha A ; Roadcap, Brad ; Zhang, Ying

BACKGROUND:

Clesrovimab (MK-1654) is an investigational, half-life extended human monoclonal antibody (mAb) against RSV F glycoprotein in clinical trials as a prophylactic agent against RSV infection for infants.

METHODS:

This adult study measured clesrovimab concentrations in the serum and nasal epithelial lining fluid (ELF) to establish the partitioning of the antibody after dosing. Clesrovimab concentrations in the nasal ELF were normalized for sampling dilution using urea concentrations from ELF and serum. Furthermore, in vitro RSV neutralization of human nasal ELF following dosing was also measured to examine the activity of clesrovimab in the nasal compartment.

FINDINGS:

mAbs with YTE mutations are reported in literature to partition ∼1-2 % of serum antibodies into nasal mucosa. Nasal: serum ratios of 1:69-1:30 were observed for clesrovimab in two separate adult human trials after urea normalization, translating to 1.4-3.3 % of serum concentrations. The nasal PK and estimates of peripheral volume of distribution correlated with higher extravascular distribution of clesrovimab. These higher concentration of the antibody in the nasal ELF corroborated with the nasal sample's ability to neutralize RSV ex vivo. An overall trend of decreased viral plaque AUC was also noted with increasing availability of clesrovimab in the nasal ELF from a human RSV challenge study.

INTERPRETATION:

Along with its extended half-life, the higher penetration of clesrovimab into the nasal epithelial lining fluid and the associated local increase in RSV neutralization activity could offer infants better protection against RSV infection.

项与 Clesrovimab 相关的新闻（医药）

2024-12-19

·echemi

Merck Submits BLA for RSV Prevention Drug, Aiming to Reduce Hospitalization Rate by Over 80%

Merck & Co. (MSD) announced today that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA), aimed at protecting infants during their first respiratory syncytial virus (RSV) season from RSV disease. The application involves the investigational preventive long-acting monoclonal antibody Clesrovimab (MK-1654). The FDA has set a review completion date before June 10, 2025. Clesrovimab is an investigational extended half-life monoclonal antibody used as a passive immunization method to prevent RSV disease. The application is based on the results of the pivotal 2b/3 clinical trial CLEVER, a randomized, placebo-controlled trial assessing the efficacy of a single dose of Clesrovimab in healthy premature and full-term infants. Additionally, this BLA includes interim results from the ongoing phase 3 clinical trial SMART, which evaluates the safety and efficacy of Clesrovimab compared to palivizumab in high-risk infants and children. Data from these trials were presented at the Infectious Diseases Week (IDWeek) conference in October 2024. Research results indicate that Clesrovimab reduced RSV-related hospitalization rates and RSV-related lower respiratory infection (LRI) hospitalization rates by 84% and over 90%, respectively, significantly lowering RSV-related hospitalization rates by over 80%.

临床3期临床结果申请上市合格传染病产品优先审批

2024-12-18

·生物制品圈

重磅！默沙东单剂量长效RSV单抗提交FDA上市申请！

周二，默克公司（北美之外称“默沙东”）宣布，美国食品药品监督管理局(FDA)已接受clesrovimab（MK-1654）的生物制品许可申请（BLA）。 FDA已将处方药使用者费用法案（PDUFA）或目标行动的日期定为2025年6月10日。默克研究实验室全球临床开发传染病和疫苗高级副总裁Paula Annunziato博士表示，如果获得批准，这将是第一个也是唯一一个针对婴儿的单剂量免疫接种，无论体重如何，旨在保护他们在第一个RSV季节期间避免获得RSV相关疾病。如果获得FDA上市许可批准，默克预计到2025年7月医生和医疗保健管理人员将可以采购clesrovimab，产品将在2025年RSV流行季及时送达。 Clesrovimab(MK-1654)是一种研究性的延长半衰期单克隆抗体（mAb），作为被动免疫用于预防RSV相关疾病。区别于赛诺菲和阿斯利康合作研发上市的Nirsevimab（国内商品名：乐唯初），Clesrovimab旨在以相同的单剂量给药，无需计算婴儿体重。并且正在健康的早产儿、足月儿和高危婴儿中进行研究，以便在他出生后的第一个RSV流行季提供直接、快速和持久的保护，防止轻度、中度和重度RSV相关疾病。该申请得到了关键性2b/3期CLEVER试验（MK-1654-004）的结果支持，在这项随机安慰剂对照试验中，评估了该产品对健康早产儿和足月婴儿（出生至1岁）给予单剂量 clesrovimab 的疗效。以及正在进行的3期SMART试验（MK-1654-007）的中期结果，同时也评估了clesrovimab与帕利珠单抗在严重RSV疾病风险增加的婴儿和儿童中的安全性和有效性。根据今年加利福尼亚州举行的IDWeek 2024期间公布的2b/3期试验中期数据，该试验的主要疗效终点：即与安慰剂相比，给药后第150天（5 个月)需要下呼吸道感染（LRI）或严重程度≥1指标的RSV相关医学就医感染（MALRI）的发生率降低60.4%（95%CI:44.1,71.9，p<0.001）。次要和第三疗效终点：与安慰剂相比，Clesrovimab在第150天之前还减少了RSV相关住院和RSV相关LRI住院（第三终点）分别降低了84.2%（95%CI:66.6,92.6，p<0.001）和 90.9%（95%CI:76.2,96.5）。Clesrovimab将严重MALRI（第三终点）的发生率降低了91.7%（95%CI:62.9,98.1）。此外在事后分析中，到第150 天，需要≥2项 LRI 指标和严重程度（MALRI 比主要 MALRI 终点更严重的终点）的MALRI发生率降低88.0%（95%CI:76.1,94.0）。讯息来源:Merck.com 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床3期疫苗临床成功申请上市临床2期

2024-12-18

·Insight数据库

只需注射一次！默沙东长效 RSV 单抗申报上市

12 月 17 日，默沙东宣布， Clesrovimab (MK-1654) 生物制品许可申请 (BLA) 已获美国 FDA 受理，用于预防婴儿呼吸道合胞病毒（RSV）感染。如果获批，这将是首个也是唯一一个针对婴儿的单剂量 RSV 单抗，无论体重如何。PDUFA 日期是 2025 年 6 月 10 日。 Clesrovimab 是一款在研的长效单克隆抗体，通过与 RSV 的融合糖蛋白结合来诱导对 RSV 的被动免疫，从而预防 RSV 感染。该上市申请基于关键 IIb/III 期 CLEVER 研究（MK-1654-004 ）和 III 期 SMART 研究（MK-1654-007）结果。 CLEVER 研究是一项随机、双盲、安慰剂对照的 IIb/III 期临床试验，旨在评估 Clesrovimab 在首次进入 RSV 季节的健康早产儿和足月婴儿中的有效性和安全性。该研究共招募了 3632 名受试者，按 2：1 的比例随机分配，接受单次固定剂量 Clesrovimab 和安慰剂治疗。结果显示，与安慰剂相比，给药后第 150 天（5 个月）RSV 相关下呼吸道感染（MALRI）发生率降低了 60.4%（95% CI：44.1, 71.9，p<0.001）。RSV 相关住院率和 RSV 相关下呼吸道感染（LRI）住院率分别降低了 84.2%（95% CI：66.6, 92.6，p<0.001）和 90.9%（95% CI：76.2, 96.5）。来源：Insight 数据库 SMART 研究是一项随机、部分盲法、多中心的 III 期临床试验，旨在评估 Clesrovimab 头对头帕博利珠单抗在患严重 RSV 疾病风险较高的婴儿和儿童中的安全性、有效性和药代动力学，共入组 901 名受试者。中期结果显示，Clesrovimab 的安全性与帕利珠单抗相当，迄今为止尚未报告任何与药物相关的严重不良反应。截至第 150 天（5 个月），Clesrovimab 和帕利珠单抗的 RSV 相关 MALRI 发生率和 RSV 相关住院率也相当。来源：Insight 数据库呼吸道合胞病毒 (RSV) 是一种传染性病毒，可引起流感等广泛的季节性感染，全球婴幼儿和老年人都深受其害。健康和高危婴儿的预防需求仍未得到满足。在全球范围内，RSV 是一岁以下健康婴儿住院的主要原因，也是中低收入国家婴儿主要死亡原因。RSV 可导致严重的呼吸道疾病，如细支气管炎和肺炎，全球每年约有 360 万人住院，10.1 万人死亡。封面来源：企业logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：月白 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

临床3期

100 项与 Clesrovimab 相关的药物交易

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外链

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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
呼吸道合胞体病毒感染	申请上市	美国	Merck Sharp & Dohme Corp.	2024-12-16
下呼吸道感染	临床3期	美国	Merck Sharp & Dohme Corp.	2021-04-07
下呼吸道感染	临床3期	美国	Werthenstein BioPharma GmbH	2021-04-07
下呼吸道感染	临床3期	美国	默沙东研发（中国）有限公司	2021-04-07
下呼吸道感染	临床3期	日本	Werthenstein BioPharma GmbH	2021-04-07
下呼吸道感染	临床3期	日本	默沙东研发（中国）有限公司	2021-04-07
下呼吸道感染	临床3期	日本	Merck Sharp & Dohme Corp.	2021-04-07
下呼吸道感染	临床3期	阿尔及利亚	Werthenstein BioPharma GmbH	2021-04-07
下呼吸道感染	临床3期	阿尔及利亚	默沙东研发（中国）有限公司	2021-04-07
下呼吸道感染	临床3期	阿尔及利亚	Merck Sharp & Dohme Corp.	2021-04-07

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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


NCT04767373 (MK-1654-004, Biospace) 人工标引	临床2/3期	呼吸道合胞体病毒感染	-	Clesrovimab	衊襯繭築觸簾廠糧廠鹹(繭觸蓋獵築獵鏇願夢窪): Difference (%) = 60.4 (95% CI, 44.1 ~ 71.9), P-Value = <0.001 更多	积极	2024-10-17
NCT04767373 (MK-1654-004, Biospace) 人工标引	临床2/3期	呼吸道合胞体病毒感染	-	Placebo		积极	2024-10-17
NCT04086472 (1654-005, CTgov)	临床2期	呼吸道合胞体病毒感染	80	RSV-A Memphis 37b	鏇膚顧繭蓋鹹廠齋壓願(觸繭鏇夢網窪積夢艱膚) = 餘艱獵衊獵廠鑰獵廠艱廠餘鑰廠鹹鹹鏇憲範衊 (鹽壓淵構遞廠築願齋獵, 構鑰構襯鹹鏇憲遞衊網 ~ 網艱簾願願襯憲衊製鬱) 更多	-	2021-04-13