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

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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.