Department of Pediatrics, Tokyo Medical and Dental University Medical Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Department of Pediatrics, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.
BMC Pediatr. 2021 Mar 2;21(1):106. doi: 10.1186/s12887-021-02567-6.
The prophylactic use of anti-respiratory syncytial virus (RSV) antibody (palivizumab) for severe RSV infection is not approved in Japan in specified groups of infants with neuromuscular diseases or other rare diseases associated with reduced ventilation competence or difficulty in expectoration, which increase the risk of exacerbation of severe RSV infection. The objective of this study is to investigate the efficacy, safety, and pharmacokinetics of palivizumab in pediatric patients with those rare diseases for which palivizumab is not indicated at present.
METHODS/DESIGN: This study is a multicenter, uncontrolled, open-label study planned to be carried out between July 1, 2019 and June 30, 2022 at 7 medical institutions in Japan. The study population will be recruited from among neonates, infants, or children aged 24 months or younger with a condition falling under any of the following 5 disease groups: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. The planned sample size is 18 subjects, including at least 3 subjects per disease group. Throughout the RSV season, at least 4 continuous doses of palivizumab will be administered intramuscularly at 15 mg/kg at intervals of 30 days. The efficacy and safety of palivizumab will be comprehensively evaluated based on the incidence of RSV-related hospitalization, and serum palivizumab concentration, serum anti-palivizumab antibody concentration, and the occurrence of adverse events/reactions after the start of palivizumab treatment.
This study will evaluate the efficacy and safety of palivizumab in pediatric patients with rare diseases which place them at high risk of severe RSV infection, but which fall outside the current indications for palivizumab prophylaxis. The generated data will have implications for the regulatory approval of prophylactic palivizumab treatment in this patient group.
This study has been prospectively registered in Japic Clinical Trials Information, which is managed and administered by the Japan Pharmaceutical Information Center (registration number: JapicCTI-194946 , registration date: September 10, 2019).
在日本，对于神经肌肉疾病或其他与通气能力降低或咳痰困难相关的罕见疾病的特定群体患儿，预防使用抗呼吸道合胞病毒（RSV）抗体（帕利珠单抗）治疗严重 RSV 感染尚未获得批准，因为这些疾病会增加严重 RSV 感染恶化的风险。本研究的目的是研究帕利珠单抗在目前未被批准用于治疗的具有这些罕见疾病的儿科患者中的疗效、安全性和药代动力学。
方法/设计：这是一项多中心、非对照、开放标签研究，计划于 2019 年 7 月 1 日至 2022 年 6 月 30 日在日本的 7 家医疗机构进行。研究人群将从患有以下 5 种疾病组之一的 24 个月或以下的新生儿、婴儿或儿童中招募：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。计划的样本量为 18 例，每个疾病组至少 3 例。在整个 RSV 季节，至少连续 4 剂帕利珠单抗将以 15mg/kg 的剂量肌肉注射，间隔 30 天。将根据 RSV 相关住院率、帕利珠单抗血清浓度、抗帕利珠单抗抗体血清浓度以及帕利珠单抗治疗开始后的不良事件/反应发生率综合评估帕利珠单抗的疗效和安全性。
本研究将评估帕利珠单抗在 RSV 感染风险较高的罕见疾病儿科患者中的疗效和安全性，但这些患者不在目前帕利珠单抗预防用药的适应证范围内。产生的数据将对该患者群体预防性帕利珠单抗治疗的监管批准产生影响。
本研究已在 Japic 临床试验信息中进行了前瞻性注册，该信息由日本药品信息中心（管理和管理）（注册号：JapicCTI-194946，注册日期：2019 年 9 月 10 日）。
