A Phase 1 Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects with stable sickle cell disease

这项研究的总体目标是评估福斯塔替尼在稳定性镰状细胞病(SCD)受试者中的临床安全性和耐受性。入选的受试者将服用福司他替尼100毫克，每日两次，共2周，然后增加到150毫克，每天2次，共4周。在整个研究过程中，受试者将被监测不良事件的体征和症状。将在特定的时间点研究福斯塔替尼对血栓炎症活性和红细胞代谢的实验室生物标记物的影响。 主要目标： 目的：评估稳定期SCD受试者服用福司他替尼的安全性和耐受性，该药是一种酪氨酸激酶抑制剂，具有抗脾酪氨酸激酶(Syk)活性。 次要目标： 通过评价药物对中性粒细胞、血小板功能和红细胞代谢的影响，了解福斯塔替尼在SCD中的作用机制，评价其抗病作用。 探索性目标： 目的：了解福斯塔替尼介导的Syk抑制细胞内信号转导的机制。 这项研究已经得到了NIH机构审查委员会的批准，并将于2023年9月开始计提。

The overall objective of this study is to assess the clinical safety and tolerability of fostamatinib in subjects with stable sickle cell disease (SCD). Subjects enrolled will receive fostamatinib 100 mg orally twice daily (BID) for 2 weeks then escalate to 150 mg orally BID for an additional four weeks. Throughout the course of the study subjects will be monitored for signs and symptoms of adverse events. The effect of fostamatinib on laboratory biomarkers of thromboinflammatory activity and red blood cell metabolism will be studied at specified timepoints. Primary Objective: To assess the clinical safety and tolerability of fostamatinib, a tyrosine kinase inhibitor with demonstrated activity against spleen tyrosine kinase (Syk), in subjects with stable SCD. Secondary Objectives: To understand the mechanisms of action of fostamatinib in SCD by evaluating the drugs effect on neutrophil and platelet function and red cell metabolism to evaluate for anti-sickling effects. Exploratory Objective: To gain insight into the mechanistic effects of fostamatinib mediated Syk inhibition on intracellular signaling. The study has been approved by the NIH Institutional Review Board and will begin accrual in September 2023.