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呼吸道合胞病毒单克隆抗体克来罗韦单抗的I期开放标签研究:中国健康受试者的安全性和耐受性

Phase I open-label study of the respiratory syncytial virus monoclonal antibody clesrovimab: Safety and tolerability in healthy Chinese participants.

作者信息

He Yulei, Zhao Fengli, Yang Xiao, Xing Shasha, Xi Feifeng, Shen Fen, Yang Lin, Ning Guijun, Sun Fang, Wang Rui, Shou Qiong, Fu Rong, Chen Chang, Sinha Anushua, Liao Xueyan

机构信息

Health Management Center, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Department of Pediatrics, Yuncheng Central Hospital of Shanxi Province, Yuncheng, Shanxi, China.

出版信息

Hum Vaccin Immunother. 2025 Dec;21(1):2516948. doi: 10.1080/21645515.2025.2516948. Epub 2025 Jul 17.

Abstract

In China, respiratory syncytial virus (RSV) is the primary cause of acute lower respiratory tract infections (LRTIs), particularly in infants and young children. Clesrovimab is a half-life‒extended RSV neutralizing monoclonal antibody for the prevention of RSV-associated LRTIs in infants. This Phase I, open-label, single-dose study, evaluated the safety and tolerability of clesrovimab in Chinese participants (EudraCT 2021-000432-58). Healthy male adults, children, and infants were sequentially enrolled in one of 3 panels, each with 25 participants. All participants received a single dose of clesrovimab (105 mg dose at 100 mg/mL concentration) on Day 1 in the deltoid or thigh muscle, beginning with male adults, followed by children, then infants, and were followed up through Day 365 postdose. Clesrovimab was generally well tolerated in healthy Chinese participants. Overall, 36.0% of male adults, 76.0% of children, and 56.0% of infants experienced at least one adverse event (AE), most were considered mild to moderate. Between Days 1 and 5 postdose, 12.0% of participants reported solicited injection site AEs (all drug-related), and 12% of infants reported solicited systemic AEs. One participant in panel A reported an anaphylaxis/hypersensitivity AE of special interest (AESI) on Day 24 postdose, not considered drug-related. No rash AESI from Day 1 through Day 42 postdose, and no serious AEs, deaths, study discontinuations or drug-related pauses were reported. These findings support the inclusion of a Chinese cohort in the global Phase IIb/III trial (NCT04767373) to evaluate the efficacy and safety of clesrovimab in healthy preterm and full-term infants.

摘要

在中国,呼吸道合胞病毒(RSV)是急性下呼吸道感染(LRTIs)的主要病因,尤其是在婴幼儿中。Clesrovimab是一种半衰期延长的RSV中和单克隆抗体,用于预防婴儿RSV相关的LRTIs。这项I期开放标签单剂量研究评估了clesrovimab在中国受试者中的安全性和耐受性(欧洲临床试验注册号2021-000432-58)。健康成年男性、儿童和婴儿依次纳入3个组中的一组,每组25名受试者。所有受试者于第1天在三角肌或大腿肌肉接受单剂量clesrovimab(浓度为100mg/mL时剂量为105mg),先从成年男性开始,然后是儿童,最后是婴儿,并在给药后365天进行随访。Clesrovimab在中国健康受试者中总体耐受性良好。总体而言,36.0%的成年男性、76.0%的儿童和56.0%的婴儿经历了至少一次不良事件(AE),大多数被认为是轻度至中度。在给药后第1天至第5天,12.0%的受试者报告了预期的注射部位AE(均与药物相关),12%的婴儿报告了预期的全身AE。A组的一名受试者在给药后第24天报告了1例特殊关注的过敏反应/超敏反应AE(AESI),不认为与药物相关。给药后第1天至第42天未出现皮疹AESI,也未报告严重AE、死亡、研究中断或与药物相关的停药情况。这些结果支持将中国队列纳入全球IIb/III期试验(NCT04767373),以评估clesrovimab在健康早产儿和足月儿中的疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2ec/12279258/25982cf86593/KHVI_A_2516948_F0001_OC.jpg

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