Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease : A Phase I Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease

Study Description: 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.Objectives: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 drug s 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.Endpoints:Primary Endpoint:To evaluate the safety and tolerability of fostamatinib as assessed by:frequency and severity of adverse events (AEs) from Baseline to Day 70Safety endpoints, including: the type, incidence, severity, and relationship to study treatment of AEs and serious adverse events (SAEs) from Baseline to Day 70 number of discontinuations due to AEs; from Baseline to Day 70Secondary Endpoints:Studies of platelet activation and aggregation at baseline, Day 14, and Day 42 following agonist exposure at 100 mg BID versus 150 mg BID of fostamatinib.Evaluate anti-sickling effects of fostamatinib through measures of red blood cell (RBC) membrane band3 tyrosine phosphorylation, RBC deformability, anti-sickling kinetics and oxygen affinity (p50).Change from baseline in intracellular reactive oxidative species (ROS) in RBCs at different doses of fostamatinib at regular time intervals (baseline, day 14, and day 42).Markers of coagulation activation at regular time intervals (baseline, day 14, and day 42) on fostamatinib and change from baseline.Exploratory Endpoints:Perform mechanistic studies of intracellular signaling pathways relevant to phosphotyrosine kinase inhibition at 100 mg BID versus 150 mg BID of fostamatinib.Measures of neutrophil activation and neutrophil extracellular trap (NET) formation at baseline and following agonistactivation at 100 mg BID versus 150 mg BID of fostamatinib..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 02. Apr. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Anemia, Sickle Cell Beta-Thalassemia Phase: Phase 1 Recruitment Status: Not yet recruiting Study Type: Interventional Thalassemia

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: June 15, 2023, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024

Study ID:	NCT05904093 10001619 001619-H
Veröffentlichungen zur Studie:

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PPN (Katalog-ID):	CTG000021024