Sickle Cell DisordersPhase 1NCT05904093
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
A Phase 1 study testing Fostamatinib in people with Sickle Cell Disorders and Sickle Cell Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sickle Cell Disorders, Sickle Cell Disease, Hemoglobin S
- What is being tested?
- Fostamatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2024to 14 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will enroll onto the study and undergo screening. Subjects who do not meet any of the following criteria during screening will not receive the study intervention but will be counted toward study accrual. Screen failures may be rescreened at a later time. In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Have provided signed written informed consent prior to performing any study procedure, including screening procedures.
- Age between 18-65 years
- Unequivocal diagnosis of SCA (HbSS or HbSBeta^0) confirmed by hemoglobin electrophoresis performed on patients at least 60 days after a blood transfusion if previously transfused.
- No transfusion in the 60 days prior to signing consent, or absence of Hb A on hemoglobin analysis (by high-performance liquid chromatography; HPLC)
- Have adequate organ function, as defined by:
Show all 15Show fewer
- Serum aspartate aminotransferase (AST) <=1.5 x Upper Limit of Normal (ULN) (unless the increased AST is assessed by the Investigator as due to hemolysis) and alanine aminotransferase (ALT) <=1.5 x ULN.
- Absolute neutrophil count >=1.5 x 10^9/L.
- Hemoglobin >= 7 g/dL
- Platelet count >=100 x 10^9/L.
- If on hydroxyurea, participant must have been on stable dose of hydroxyurea (defined as a stable dose for at least 3 months and inclusive of dose modifications for hematological toxicity per PI discretion) prior to signing consent.
- For women of reproductive potential, have a negative serum pregnancy test during the screening period. Women of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not been naturally postmenopausal (i.e., who have not menstruated at all for at least the preceding 1 year prior to signing informed consent unrelated to hormonal contraception).
- For women of reproductive potential as well as men and their partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 effective forms of contraception from the time of giving informed consent, during the study, and for 28 days (both men and women) following the last dose of study treatment. An effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine or subdermal contraceptive implants, and barrier methods.
- Be willing to comply with all study procedures for the duration of the study.
- Must be able to provide consent
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pain crisis requiring parenteral treatment within 14 days of signing consent.
- Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data. Such significant medical conditions include, but are not limited to the following:
- History of neutropenia (benign ethnic neutropenia and/or acquired neutropenia related to drug suppression by hydroxyurea and/or cyclic hematopoiesis are permitted).
- History of posterior reversible encephalopathy syndrome (PRES)
- History of poorly controlled hypertension (defined as systolic blood pressure >=130 mmHg or average diastolic blood pressure >=90 mmHg based on an average of 3 blood pressure readings despite adequate antihypertensive therapy) unless controlled for >90 days prior to enrollment.
Show all 18Show fewer
- Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptase-polymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
- History of drug-induced cholestatic hepatitis.
- History of any primary malignancy.
- Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count <400/microliter and viral load >100,000 copies/ml) on antiretroviral therapy.
- Current or recent history of psychiatric disorder that, in the opinion of the Investigator or Medical Monitor, could compromise the ability of the subject to cooperate with study visits and procedures.
- Are currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo.
- Use of newly approved SCD therapy (L-glutamine or crizanlizumab) is NOT permitted on this study. Subjects who have received newly approved SCD therapy in the 7 days prior to signing consent will be excluded.
- Having had a prior bone marrow or stem cell transplant.
- Currently pregnant or lactating.
- Currently receiving strong inhibitors of CYP3A4/5 that have not been stopped for >=5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of CYP3A4 that have not been stopped for >=28 days or a time frame equivalent to 5 half-lives (whichever is longer), prior to signing consent. SCD patients that are receiving treatment with CYP3A4 substrate drugs, some BCRP substrate drugs (eg. rosuvastatin), and some P-glycoprotein substrate drugs (eg. Digoxin) are excluded from the study.
- Currently receiving erythropoiesis stimulating agents.
- Has received fostamatinib in 3 months prior to signing consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222, prpl@cc.nih.gov
About this study
Official title: A Phase I Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
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.
Read more
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.
Read the 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 in cohort 1 will receive fostamatinib 100 mg orally twice daily (BID) for 2 weeks then escalate to 150 mg orally BID for an additional four weeks. Subjects enrolled in cohort 2 will receive fostamatinib 100 mg orally once daily (QD) for 2 weeks then escalate to 150 mg orally QD for an additional four weeks. Cohort 2 will allow the subjects from cohort 1 the option to re-enroll to undergo the QD dosing regimen. 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 inflammatory 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 (Cohort 1).
To evaluate anti-sickling and anti-inflammatory effects of fostamatinib in SCD via neutrophil function and red cell metabolism (Cohort 2).
Exploratory Objectives:
To gain insight into the exposure response and mechanistic effects of fostamatinib mediated Syk inhibition on intracellular signaling.
Compare anti-sickling and anti-inflammatory effects of fostamatinib between 2 dose regimens.
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:
- Neutrophil activation and NETosis at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- 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) at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- Change from baseline in intracellular reactive oxidative species (ROS) in RBCs at different doses of fostamatinib at regular time intervals (baseline, days 14, 43 and end of study).
- 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 on 100 mg BID and 150 mg BID (Cohort 1)
Exploratory Endpoints:
- Proteomic, metabolomic and lipidomic studies to evaluate the effect of fostamatinib on RBCs and monocytes at regular time intervals (baseline, days 14, 43 and end of study).
- Studies of extracellular vesicles (EVs) at regular time intervals (baseline, days 14, 43 and end of study).
- Measures of neutrophil activation and neutrophil extracellular trap (NET) formation at baseline and following agonistactivation Z
- Compare fostamatinib at different doses on secondary and exploratory endpoints by comparing data from subjects who have received both dose levels.
- Conditions
- Sickle Cell Disorders, Sickle Cell Disease, Hemoglobin S, Hb-SS Disease, Disease Sickle Cell Anemia
- Being tested
- Fostamatinib
- Keywords
- Sickle Cell, Tyrosine Kinase Inhibitor, Fostamatinib
- Medical subject headings
- Anemia, Sickle Cell, Sickle Cell Trait
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FostamatinibDrug
Fostamatinib will be administered orally for 6 weeks. Dosing will begin at 100 mg and increase to 150 mg after 2 weeks. The dosing frequency will be once daily or twice daily, depending on cohort assignment.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Fostamatinib 100 mg BID - 150 mg BID | Experimental | Cohort 1: Four participants with sickle cell disease will receive fostamatinib 100 mg orally twice daily for 2 weeks, followed by 150 mg orally twice daily for 4 weeks. Receives: Drug: Fostamatinib |
| Cohort 2: Fostamatinib 100 mg QD - 150 mg QD Cohort 2 re-enrollment subgroup | Experimental | Up to 19 participants with sickle cell disease, including at least 15 treatment-naive participants and up to 4 participants from Cohort 1 who elect to continue under the revised dosing regimen, will receive fostamatinib 100 mg orally once daily for 2 weeks, followed by 150 mg orally once daily for 4 weeks.Up to 4 participants who previously completed Cohort 1 may re-enroll in Cohort 2 after a 3-month washout period. These participants receive the QD regimen and may be compared with their prior BID exposure in an exploratory, hypothesis-generating analysis. Receives: Drug: Fostamatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of fostamatinib
Assess the frequency, type, severity, and relationship to fostamatinib of adverse events (AEs) and serious adverse events (SAEs); the number of participants who discontinue treatment because of AEs; and changes over time from baseline in clinical laboratory measures, including serum chemistry, liver function, hematology, and coagulation parameters. Specific laboratory measures include hemoglobin, reticulocyte count, bilirubin, lactate dehydrogenase, white blood cell count, absolute neutrophil count, and platelet count.
Measured: From baseline through Day 70 (end-of-study follow-up; approximately 28 days after the final dose)
Secondary outcomes (10)
Time to 50% sickling (t50)
Measure the time required for 50% of red blood cells to sickle under ex vivo conditions as an indicator of anti-sickling activity.
Measured: Baseline, Day 14, Day 43, and Day 70
Percentage of sickled red blood cells
Assess the percentage of sickled cells under normal and hypoxic ex vivo conditions and evaluate change from baseline.
Measured: Baseline, Day 14, Day 43, and Day 70
Neutrophil activation and NETosis
Measure changes from baseline in neutrophil activation and neutrophil extracellular trap formation during fostamatinib treatment.
Measured: Baseline, Day 14, Day 43, and end of study/Day 70
RBC Band 3 tyrosine
Evaluate the effect of fostamatinib on tyrosine phosphorylation of the RBC membrane Band 3 protein, a marker related to RBC membrane integrity and sickling biology.
Measured: Baseline, Day 14, Day 43, and Day 70
RBC deformability
Baseline, Day 14, Day 43, and Day 70
Measured: Baseline, Day 14, Day 43, and Day 70
Anti-sickling kinetics
Characterize the kinetics of RBC sickling under ex vivo conditions and determine whether fostamatinib alters sickling behavior.
Measured: Baseline, Day 14, Day 43, and Day 70
Oxygen affinity of hemoglobin (p50)
Measure the oxygen tension at which hemoglobin is 50% saturated to evaluate treatment-related changes in RBC oxygen-binding properties.
Measured: Baseline, Day 14, Day 43, and Day 70
Measure the oxygen tension at which hemoglobin is 50% saturated to evaluate treatment-related changes in RBC oxygen-binding properties.
Assess change from baseline in intracellular oxidative stress in RBCs at the different fostamatinib dose levels.
Measured: Baseline, Day 14, Day 43, and Day 70
R406 exposure and pharmacodynamic effects
Determine peak plasma levels of R406, the active fostamatinib metabolite, and correlate exposure with inhibition of NETosis, Band 3 tyrosine phosphorylation, RBC effects, and sickling kinetics.
Measured: Cohort 1: baseline, 1, 2, 4, and 8 hours after dosing on Days 0 and 14
Dose-regimen comparison
Exploratorily compare secondary biomarker outcomes between the BID regimen in Cohort 1 and the QD regimen in Cohort 2, including within-participant comparisons for participants who complete both regimens.
Measured: Across the treatment period and scheduled assessment visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start18 Dec 2024
- Primary completion14 May 2027 (estimated)
- Study completion14 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DisordersStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Swee Lay Thein, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05904093
- Sponsor's protocol ID
- 10001619
- Other IDs
- 001619-H
- Status last verified
- 29 Oct 2026
- First submitted
- 13 Jun 2023
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT05904093
- Acronym / sponsor ID
- 10001619
- Conditions
- Sickle Cell Disorders, Sickle Cell Disease, Hemoglobin S, Hb-SS Disease, Disease Sickle Cell Anemia
- Keywords
- Sickle Cell, Tyrosine Kinase Inhibitor, Fostamatinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 18 Dec 2024 (actual)
- Primary completion
- 14 May 2027 (estimated)
- Study completion
- 14 May 2027 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 in cohort 1 will receive fostamatinib 100 mg orally twice daily (BID) for 2 weeks then escalate to 150 mg orally BID for an additional four weeks. Subjects enrolled in cohort 2 will receive fostamatinib 100 mg orally once daily (QD) for 2 weeks then escalate to 150 mg orally QD for an additional four weeks. Cohort 2 will allow the subjects from cohort 1 the option to re-enroll to undergo the QD dosing regimen. 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 inflammatory 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 (Cohort 1).
To evaluate anti-sickling and anti-inflammatory effects of fostamatinib in SCD via neutrophil function and red cell metabolism (Cohort 2).
Exploratory Objectives:
To gain insight into the exposure response and mechanistic effects of fostamatinib mediated Syk inhibition on intracellular signaling.
Compare anti-sickling and anti-inflammatory effects of fostamatinib between 2 dose regimens.
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:
- Neutrophil activation and NETosis at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- 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) at regular time intervals (baseline, days 14, 43, and end of study) on fostamatinib and change from baseline.
- Change from baseline in intracellular reactive oxidative species (ROS) in RBCs at different doses of fostamatinib at regular time intervals (baseline, days 14, 43 and end of study).
- 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 on 100 mg BID and 150 mg BID (Cohort 1)
Exploratory Endpoints:
- Proteomic, metabolomic and lipidomic studies to evaluate the effect of fostamatinib on RBCs and monocytes at regular time intervals (baseline, days 14, 43 and end of study).
- Studies of extracellular vesicles (EVs) at regular time intervals (baseline, days 14, 43 and end of study).
- Measures of neutrophil activation and neutrophil extracellular trap (NET) formation at baseline and following agonistactivation Z
- Compare fostamatinib at different doses on secondary and exploratory endpoints by comparing data from subjects who have received both dose levels.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Fostamatinib 100 mg BID - 150 mg BID | Experimental | Drug: FostamatinibCohort 1: Four participants with sickle cell disease will receive fostamatinib 100 mg orally twice daily for 2 weeks, followed by 150 mg orally twice daily for 4 weeks. |
| Cohort 2: Fostamatinib 100 mg QD - 150 mg QD Cohort 2 re-enrollment subgroup | Experimental | Drug: FostamatinibUp to 19 participants with sickle cell disease, including at least 15 treatment-naive participants and up to 4 participants from Cohort 1 who elect to continue under the revised dosing regimen, will receive fostamatinib 100 mg orally once daily for 2 weeks, followed by 150 mg orally once daily for 4 weeks.Up to 4 participants who previously completed Cohort 1 may re-enroll in Cohort 2 after a 3-month washout period. These participants receive the QD regimen and may be compared with their prior BID exposure in an exploratory, hypothesis-generating analysis. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects will enroll onto the study and undergo screening. Subjects who do not meet any of the following criteria during screening will not receive the study intervention but will be counted toward study accrual. Screen failures may be rescreened at a later time. In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Have provided signed written informed consent prior to performing any study procedure, including screening procedures.
- Age between 18-65 years
- Unequivocal diagnosis of SCA (HbSS or HbSBeta^0) confirmed by hemoglobin electrophoresis performed on patients at least 60 days after a blood transfusion if previously transfused.
- No transfusion in the 60 days prior to signing consent, or absence of Hb A on hemoglobin analysis (by high-performance liquid chromatography; HPLC)
Key exclusion criteria (18 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pain crisis requiring parenteral treatment within 14 days of signing consent.
- Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data. Such significant medical conditions include, but are not limited to the following:
- Has received fostamatinib in 3 months prior to signing consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FostamatinibFostamatinib will be administered orally for 6 weeks. Dosing will begin at 100 mg and increase to 150 mg after 2 weeks. The dosing frequency will be once daily or twice daily, depending on cohort assignment. | Drug | Cohort 1: Fostamatinib 100 mg BID - 150 mg BID, Cohort 2: Fostamatinib 100 mg QD - 150 mg QD Cohort 2 re-enrollment subgroup |
Primary outcome
Safety and tolerability of fostamatinib
Time frame: From baseline through Day 70 (end-of-study follow-up; approximately 28 days after the final dose)
Assess the frequency, type, severity, and relationship to fostamatinib of adverse events (AEs) and serious adverse events (SAEs); the number of participants who discontinue treatment because of AEs; and changes over time from baseline in clinical laboratory measures, including serum chemistry, liver function, hematology, and coagulation parameters. Specific laboratory measures include hemoglobin, reticulocyte count, bilirubin, lactate dehydrogenase, white blood cell count, absolute neutrophil count, and platelet count.
10 secondary outcomes
Time to 50% sickling (t50)
Time frame: Baseline, Day 14, Day 43, and Day 70
Percentage of sickled red blood cells
Time frame: Baseline, Day 14, Day 43, and Day 70
Neutrophil activation and NETosis
Time frame: Baseline, Day 14, Day 43, and end of study/Day 70
RBC Band 3 tyrosine
Time frame: Baseline, Day 14, Day 43, and Day 70
RBC deformability
Time frame: Baseline, Day 14, Day 43, and Day 70
Anti-sickling kinetics
Time frame: Baseline, Day 14, Day 43, and Day 70
Oxygen affinity of hemoglobin (p50)
Time frame: Baseline, Day 14, Day 43, and Day 70
Measure the oxygen tension at which hemoglobin is 50% saturated to evaluate treatment-related changes in RBC oxygen-binding properties.
Time frame: Baseline, Day 14, Day 43, and Day 70
R406 exposure and pharmacodynamic effects
Time frame: Cohort 1: baseline, 1, 2, 4, and 8 hours after dosing on Days 0 and 14
Dose-regimen comparison
Time frame: Across the treatment period and scheduled assessment visits
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Sickle Cell Disorders
Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis
RecruitingPhase 2
Safety of Anumigilimab (CSL324) in Adults With Sickle Cell Disease (SCD)
Sickle Cell Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Swee Lay Thein, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fostamatinib in people with Sickle Cell Disorders and Sickle Cell Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jordan B Branch ((301) 221-3820, jordan.branch@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of fostamatinib (time frame: From baseline through Day 70 (end-of-study follow-up; approximately 28 days after the final dose)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.