帕利珠单抗用于治疗标签外有严重呼吸道合胞病毒感染风险的新生儿、婴儿及幼儿的安全性、有效性和药代动力学：一项多中心II期临床试验

Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial.

作者信息

Mori Masaaki, Yoshizaki Kanako, Watabe Shinichi, Ishige Mika, Hinoki Akinari, Kondo Takuya, Taguchi Tomoaki, Hasegawa Hisaya, Hatata Tomoko, Tanuma Naoyuki, Kirino Kosuke, Hirakawa Akihiro, Naruto Takuya, Imai Minoru, Koike Ryuji, Hosoi Kenichiro, Kusuda Satoshi

机构信息

Department of Pediatrics, Tokyo Medical and Dental University Medical Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

出版信息

Lancet Reg Health West Pac. 2023 Jul 26;39:100847. doi: 10.1016/j.lanwpc.2023.100847. eCollection 2023 Oct.

DOI:10.1016/j.lanwpc.2023.100847

PMID:37554997

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10405310/

Abstract

BACKGROUND

Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan.

METHODS

This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days.

FINDINGS

Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period.

INTERPRETATION

Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study.

FUNDING

Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.

摘要

背景

患有某些罕见疾病的儿科患者发生严重呼吸道合胞病毒（RSV）感染的风险增加。然而，目前在日本，这些患者中不建议预防性使用抗RSV抗体（帕利珠单抗）。

方法

这项全球首例多中心、非对照、开放标签的II期临床试验于2019年7月28日至2021年9月24日在日本的7家医疗机构进行，以研究帕利珠单抗在23名从患有以下任何一种疾病的新生儿、婴儿或24个月及以下儿童中招募的受试者中的疗效、安全性和药代动力学：肺发育不全、气道狭窄、先天性食管闭锁、遗传性代谢疾病或神经肌肉疾病。以15mg/kg的剂量，每30天肌肉注射至少四剂帕利珠单抗。

结果

23名入组受试者完成了研究。没有受试者因RSV需要住院治疗。不良事件（AE）与最新访谈表中描述的事件术语没有显著差异。5例严重不良事件需要非计划住院，但在未发生RSV感染的情况下得到缓解。在整个研究期间，帕利珠单抗的治疗有效浓度得以维持。

解读

帕利珠单抗在预防严重RSV感染导致的严重呼吸道症状和住院方面可能耐受性良好且有效，表明可在本研究纳入的儿科患者中进行预防性使用。

资助

日本医疗研究与开发机构（AMED），资助编号19lk0201097h0001（授予MM）、20lk0201097h0002（授予MM）、21lk0201097h0003（授予MM）和22lk0201097h0004（授予MM）。AMED在本研究的实施、数据的分析和解读或提交结果的决定中没有任何作用。