Department of Pediatrics, Nara Medical University, Kashihara, Japan
Department of Joint Surgery, IMSUT Hospital, The University of Tokyo, Tokyo, Japan.
BMJ Open. 2022 Jun 13;12(6):e059667. doi: 10.1136/bmjopen-2021-059667.
Persons with haemophilia A (PwHA) commonly experience regular bleeding into joints, which may result in joint damage and complications such as degenerative arthritis. Emicizumab has previously demonstrated efficacy in reducing the occurrence of joint bleeds and target joints, along with having a favourable safety profile; however, data on the long-term effects on joint health are lacking. The AOZORA study will evaluate the long-term safety and joint health of paediatric PwHA without factor (F)VIII inhibitors taking emicizumab; here, we report the details of the study protocol and baseline data.
AOZORA is a multicentre, open-label, phase IV clinical study in Japan that aims to enrol approximately 30 PwHA aged <12 years without FVIII inhibitors. The primary endpoints include a long-term safety evaluation of adverse events, laboratory test abnormalities and FVIII inhibitor development; and a long-term joint health assessment using MRI and the Hemophilia Joint Health Score. Exploratory endpoints include characterising participants' physical activities and the number of activity-related bleeds requiring coagulation factor treatment. Currently, 30 participants have been enrolled, including 20 emicizumab-naïve participants and 10 who transferred from HOHOEMI, a previous study in paediatric PwHA.
The AOZORA study was approved by the Institutional Review Boards of Nara Medical University and the St Marianna University Group. The study will be conducted in compliance with the Declaration of Helsinki, the standards stipulated in paragraph 3 of Article 14 and Article 80-2 of the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act, the Ministerial Ordinance on Good Clinical Practice and the Ministerial Ordinance on Good Post-marketing Study Practice. Data will be published in peer-reviewed journals and presented at Global congresses.
JapicCTI-194701.
患有血友病 A（PwHA）的人通常会经常出现关节内出血，这可能导致关节损伤和退行性关节炎等并发症。依库珠单抗先前已被证明可有效减少关节出血和靶关节的发生，且具有良好的安全性；然而，缺乏关于其对关节健康长期影响的数据。AOZORA 研究将评估无因子（F）VIII 抑制剂的接受依库珠单抗治疗的儿科 PwHA 的长期安全性和关节健康；在这里，我们报告研究方案和基线数据的详细信息。
AOZORA 是日本的一项多中心、开放标签、IV 期临床研究，旨在招募约 30 名无 FVIII 抑制剂的年龄<12 岁的 PwHA。主要终点包括对不良事件、实验室检查异常和 FVIII 抑制剂发展的长期安全性评估；以及使用 MRI 和血友病关节健康评分对长期关节健康进行评估。探索性终点包括描述参与者的身体活动和需要凝血因子治疗的与活动相关出血的次数。目前，已有 30 名参与者入组，包括 20 名依库珠单抗初治参与者和 10 名从 HOHOEMI 转入的参与者，HOHOEMI 是一项针对儿科 PwHA 的先前研究。
AOZORA 研究已获得奈良医科大学和 St Marianna 大学集团机构审查委员会的批准。该研究将遵守赫尔辛基宣言、第 14 条第 3 款和《药品、医疗器械和其他治疗产品法》第 80-2 条规定的标准、《良好临床实践部长令》和《良好上市后研究实践部长令》。数据将在同行评议的期刊上发表，并在全球大会上展示。
JapicCTI-194701。
