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

评估 Fostamatinib 剂量递增对稳定镰状细胞病受试者的安全性和耐受性的 1 期研究

• 批准号: 10930552
• 负责人: Arun Shet
• 金额: $ 11.44万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10930552
• 关键词: Adverse event; Biological Markers; Cellular Metabolic Process; Clinical; Dose; Enrollment; Erythrocytes; Goals; Individual; Institutional Review Boards; Laboratories; Mediating; Monitor; Oral; Pharmaceutical Preparations; Phase I Clinical Trials; Phosphotransferases; Phosphotyrosine; SYK gene; Safety; Sickle Cell Anemia; Signal Pathway; Signal Transduction; Signs and Symptoms; Specific qualifier value; Study Subject; Tyrosine Kinase Inhibitor; United States National Institutes of Health; immune activation; insight; neutrophil; novel; phase 1 study; platelet function; safety assessment; sickling; thromboinflammation

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.

本研究的总体目的是评估福他替尼在稳定型镰状细胞病（SCD）受试者中的临床安全性和耐受性。 入组的受试者将接受fostamatinib 100 mg口服，每日两次（BID），持续2周，然后递增至150 mg口服BID，持续另外4周。在整个研究过程中，将监测受试者的不良事件体征和症状。将在特定时间点研究福他替尼对血栓炎症活性和红细胞代谢的实验室生物标志物的影响。 主要目的： 在稳定型SCD受试者中评估fostamatinib（一种已证实对脾酪氨酸激酶（Syk）具有活性的酪氨酸激酶抑制剂）的临床安全性和耐受性。 次要目的： 通过评价药物对中性粒细胞和血小板功能以及红细胞代谢的影响，了解福他替尼在SCD中的作用机制，以评价抗镰状化作用。 探索性目的： 深入了解福他替尼介导的Syk抑制对细胞内信号传导的机制作用。 该研究已获得NIH机构审查委员会的批准，将于2023年9月开始招募。