Ignite Creation Date:
2025-12-25 @ 1:02 AM
Ignite Modification Date:
2026-01-04 @ 4:40 AM
Study NCT ID:
NCT05904093
Status:
RECRUITING
Last Update Posted:
2025-09-15
First Post:
2023-06-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Organization:
Study Overview
Official Title:
A Phase I Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Status:
RECRUITING
Status Verified Date:
2025-08-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Sickle cell disease (SCD) is a genetic disease that causes the body to produce abnormal ( sickled ) red blood cells. SCD can cause anemia and life-threatening complications in the lungs, heart, kidney, and nerves. People with SCD are also at increased risk of forming blood clots in the veins and lungs, but the standard treatments for these clots can cause increased bleeding in people with SCD. Better treatments are needed.
Objective:
To test a drug (fostamatinib) in people with SCD.
Eligibility:
People aged 18 to 65 with SCD.
Design:
Participants will have 6 clinic visits over 12 weeks. Each visit will be 2 to 3 hours.
Participants will be screened. They will have a physical exam with blood tests. They will tell the researchers about the medications they take.
Fostamatinib is a tablet taken by mouth. Participants will take the drug at home, twice a day, for up to 6 weeks.
Participants will have a clinic visit every 2 weeks while they are taking the drug. At each visit they will have a physical exam with blood tests. They will talk about any side effects the drug may be causing. If they are tolerating the drug well after the first 2 weeks, they may begin taking a higher dose.
Participants will have a final visit 4 weeks after they stop taking the drug. They will have a physical exam and blood tests; they will be checked for any side effects of the drug.
Sickle cell disease (SCD) is a genetic disease that causes the body to produce abnormal ( sickled ) red blood cells. SCD can cause anemia and life-threatening complications in the lungs, heart, kidney, and nerves. People with SCD are also at increased risk of forming blood clots in the veins and lungs, but the standard treatments for these clots can cause increased bleeding in people with SCD. Better treatments are needed.
Objective:
To test a drug (fostamatinib) in people with SCD.
Eligibility:
People aged 18 to 65 with SCD.
Design:
Participants will have 6 clinic visits over 12 weeks. Each visit will be 2 to 3 hours.
Participants will be screened. They will have a physical exam with blood tests. They will tell the researchers about the medications they take.
Fostamatinib is a tablet taken by mouth. Participants will take the drug at home, twice a day, for up to 6 weeks.
Participants will have a clinic visit every 2 weeks while they are taking the drug. At each visit they will have a physical exam with blood tests. They will talk about any side effects the drug may be causing. If they are tolerating the drug well after the first 2 weeks, they may begin taking a higher dose.
Participants will have a final visit 4 weeks after they stop taking the drug. They will have a physical exam and blood tests; they will be checked for any side effects of the drug.
Detailed Description:
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 assess the pharmacokinetics of fostamatinib in SCD and correlate drug exposure to effects on neutrophil, platelet function, and red cell metabolism to evaluate for anti-sickling and anti-inflammatory effects.
Exploratory Objective:
To gain insight into the exposure response and 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 70
* Safety 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 70
* results of clinical laboratory tests over time and change from baseline (e.g., serum chemistry, liver function test, hematology, coagulation)
Secondary Endpoints:
* Studies of platelet activation and aggregation at baseline, Day 14 following agonist exposure at 100 mg BID, and Day 43 following agonist exposure at 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 43).
* Markers of coagulation activation at regular time intervals (baseline, day 14, and day 43) on fostamatinib and change from baseline.
* Determine peak R406 levels and assess correlation of R406 exposure with inhibition of NETosis and its effect on red blood cell membrane band 3 tyrosine phosphorylation and sickling kinetics at baseline, 1 hr, 2 hrs, 4 hrs, and 8 hrs post dosing (100 mg BID and 150 mg BID)
Exploratory Endpoints:
* Perform mechanistic studies of intracellular signaling pathways relevant to phosphotyrosine kinase inhibition on Day 14 following agonist exposure at 100 mg BID and Day 43 following agonist exposure at 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.
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 assess the pharmacokinetics of fostamatinib in SCD and correlate drug exposure to effects on neutrophil, platelet function, and red cell metabolism to evaluate for anti-sickling and anti-inflammatory effects.
Exploratory Objective:
To gain insight into the exposure response and 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 70
* Safety 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 70
* results of clinical laboratory tests over time and change from baseline (e.g., serum chemistry, liver function test, hematology, coagulation)
Secondary Endpoints:
* Studies of platelet activation and aggregation at baseline, Day 14 following agonist exposure at 100 mg BID, and Day 43 following agonist exposure at 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 43).
* Markers of coagulation activation at regular time intervals (baseline, day 14, and day 43) on fostamatinib and change from baseline.
* Determine peak R406 levels and assess correlation of R406 exposure with inhibition of NETosis and its effect on red blood cell membrane band 3 tyrosine phosphorylation and sickling kinetics at baseline, 1 hr, 2 hrs, 4 hrs, and 8 hrs post dosing (100 mg BID and 150 mg BID)
Exploratory Endpoints:
* Perform mechanistic studies of intracellular signaling pathways relevant to phosphotyrosine kinase inhibition on Day 14 following agonist exposure at 100 mg BID and Day 43 following agonist exposure at 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.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 001619-H | None | None | View |