Ignite Creation Date:
2024-05-06 @ 7:07 PM
Last Modification Date:
2024-10-26 @ 3:01 PM
Study NCT ID:
NCT05904093
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-07-15
First Post:
2023-06-13
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:
National Institutes of Health Clinical Center CC
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:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-10-22
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 eg 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 42 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 42
Markers of coagulation activation at regular time intervals baseline day 14 and day 42 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 42 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 eg 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 42 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 42
Markers of coagulation activation at regular time intervals baseline day 14 and day 42 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 42 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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001619-H | None | None | None |