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日本第一阶段研究全球抗TL1A抗体发展PF-06480605:一个随机,安慰剂控制,单次上升剂量研究
Kei Fukuhara1, Srividya Neelakantan2, Kenichi Furihata3
1Pfizer R&D Japan, Tokyo, Japan.
Clinical and translational science
|March 11, 2025
概括
针对TL1A的单克隆抗体PF-06480605在日本成年人中显示出良好的安全性和药理动力学. 这支持其在日本和中国的炎症性肠病的发展.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
背景情况:
- PF-06480605是一种IgG1单克隆抗体,向瘤缩因子α类干1A (TL1A).
- 之前的1/2a期研究表明可接受的安全性和炎症性肠病 (IBD) 的潜在疗效.
- 一个日本本地第一阶段研究旨在满足监管要求并促进日本和中国的发展.
研究的目的:
- 评估PF-06480605在日本健康成年人中的安全性,耐受性,免疫性,药理动力学 (PK) 和药理动力学.
- 为了满足未来临床开发的日本监管要求.
- 为中国当地第一阶段研究设计提供信息,加快全球发展.
主要方法:
- 第1期,随机,双盲,安慰剂控制,单剂量升级研究.
- 日本的健康成年人接受PF-06480605 (150毫克或450毫克) 或安慰剂的单次皮下注射剂量.
- 评估了安全性,耐受性,免疫性,PK和药学动力学,包括血清TL1A水平.
主要成果:
- 在不同剂量水平上,PF-06480605的耐受性很好.
- 观察到缓慢吸收,平均Tmax为217.5小时,半衰期长 (平均t1/2为18.4-19.1天).
- 观察到剂量相对应的暴露,没有种族的PK差异,以及血清TL1A水平的剂量依赖性增加. 免疫性是100%的.
结论:
- 该研究符合日本的监管要求.
- 450毫克剂量的良好的耐受性和PK支持在中国研究中的150毫克队列的豁免.
- PF-06480605显示了适合IBD进一步发展的特征.
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