ClinicalTrials.gg
Sign In
RecruitingNCT05904093Updated Nov 5, 2026

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

A Phase 1 interventional study of Fostamatinib in Sickle Cell Disorders, Sickle Cell Disease and Hemoglobin S, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-11-05.

Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 1, Interventional, and Basic science

From the registry’s dates

  • Started Dec 2024; still recruiting 1 year 10 months later.
Updated Nov 2, 2026Eligibility revisedGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
35
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

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.
02

Conditions studied

  • Sickle Cell Disorders
  • Sickle Cell Disease
  • Hemoglobin S
  • Hb-SS Disease
  • Disease Sickle Cell Anemia

Keywords

  • Sickle Cell
  • Tyrosine Kinase Inhibitor
  • Fostamatinib
03

In context

Anemia, Sickle Cell

1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.

This study's planned enrollment of 35 is below the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.

Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.

Browse National Heart, Lung, and Blood Institute (NHLBI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

The criteria were revised on the registry on Nov 2, 2026. See what changed

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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:

  1. Have provided signed written prior to performing any study procedure, including screening procedures.
  2. Age between 18-65 years
  3. Unequivocal diagnosis of SCA (HbSS or HbSBeta\^0) confirmed by electrophoresis performed on patients at least 60 days after a blood transfusion if previously transfused.
  4. No transfusion in the 60 days prior to signing consent, or absence of Hb A on hemoglobin analysis (by high-performance liquid chromatography; HPLC)

  5. Have adequate organ function, as defined by:

    1. Serum (AST) \<=1.5 x (ULN) (unless the increased AST is assessed by the Investigator as due to hemolysis) and alanine aminotransferase (ALT) \<=1.5 x ULN.
    2. >=1.5 x 10\^9/L.
    3. Hemoglobin >= 7 g/dL
    4. count >=100 x 10\^9/L.
  6. 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.
  7. For women of , 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 (i.e., who have not menstruated at all for at least the preceding 1 year prior to signing informed consent unrelated to hormonal ).
  8. 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.
  9. Be willing to comply with all study procedures for the duration of the study.
  10. Must be able to provide consent

Exclusion criteria

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Pain crisis requiring parenteral treatment within 14 days of signing consent.

  2. 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:

    1. History of neutropenia (benign ethnic neutropenia and/or acquired neutropenia related to drug suppression by hydroxyurea and/or cyclic hematopoiesis are permitted).
    2. History of posterior reversible encephalopathy syndrome (PRES)
    3. 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.
    4. Active viral infection as evidenced by testing positive for surface antigen or 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.
    5. History of drug-induced cholestatic hepatitis.
    6. History of any primary .
    7. Testing positive for 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.
    8. 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.
    9. Are currently enrolled in another therapeutic clinical trial involving ongoing therapy with any or marketed product or placebo.
    10. 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.
    11. Having had a prior bone marrow or stem cell transplant.
    12. Currently pregnant or lactating.
    13. Currently receiving strong inhibitors of /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.
    14. Currently receiving erythropoiesis stimulating agents.
  3. Has received fostamatinib in 3 months prior to signing consent
Terms in these criteria, in plain language(15)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
35 participants (estimated)

Study arms

  • Experimental
    Cohort 1: Fostamatinib 100 mg BID - 150 mg BID

    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.

    Drug: Fostamatinib

  • Experimental
    Cohort 2: Fostamatinib 100 mg QD - 150 mg QD Cohort 2 re-enrollment subgroup

    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.

    Drug: Fostamatinib

Interventions

  • DrugFostamatinib

    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.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From baseline through Day 70 (end-of-study follow-up; approximately 28 days after the final dose)

Secondary outcomes

  1. 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.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  2. Percentage of sickled red blood cells

    Assess the percentage of sickled cells under normal and hypoxic ex vivo conditions and evaluate change from baseline.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  3. Neutrophil activation and NETosis

    Measure changes from baseline in neutrophil activation and neutrophil extracellular trap formation during fostamatinib treatment.

    Time frame: Baseline, Day 14, Day 43, and end of study/Day 70

  4. 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.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  5. RBC deformability

    Baseline, Day 14, Day 43, and Day 70

    Time frame: Baseline, Day 14, Day 43, and Day 70

  6. Anti-sickling kinetics

    Characterize the kinetics of RBC sickling under ex vivo conditions and determine whether fostamatinib alters sickling behavior.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  7. 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.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  8. 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.

    Time frame: Baseline, Day 14, Day 43, and Day 70

  9. 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.

    Time frame: Cohort 1: baseline, 1, 2, 4, and 8 hours after dosing on Days 0 and 14

  10. 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.

    Time frame: Across the treatment period and scheduled assessment visits

07

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • NIH Clinical Center Office of Patient Recruitment (OPR) · Contactprpl@cc.nih.gov · 800-411-1222
08

References and documents

Individual participant data

Plan to share: Undecided

09

Timeline

4 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Dec 2024 (actual). Primary completion is estimated for May 2027, 28 months after the start.

Of 58 phase 1 interventional studies under Anemia, Sickle Cell, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 65. This study's planned 28 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 13, 2023
First posted
Jun 15, 2023
StartActual
Dec 18, 2024
Primary completionEst.
May 14, 2027
CompletionEst.
May 14, 2027
Last update
Nov 5, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Eligibility
1 inclusion criterion added; 1 exclusion criterion edited
What changed in the criteria
Inclusion criteria
  • AddedMust be able to provide consent
Exclusion criteria
  • EditedHas not received fostamatinib in 3 months prior to signing consent
Nov 2, 2026
Show all 4 updates
  1. Nov 5, 2026
    Minor edits only
    + 1 other change: verification date
  2. Nov 2, 2026
    Eligibility 1 inclusion criterion added; 1 exclusion criterion edited
    What changed in the criteria
    Inclusion criteria
    • AddedMust be able to provide consent
    Exclusion criteria
    • EditedHas not received fostamatinib in 3 months prior to signing consent
    + 1 other change: description
  3. Oct 30, 2026
    Minor edits only
    + 1 other change: verification date
  4. Oct 8, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT05904093
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Sponsor
First posted
Jun 15, 2023
Start date
Dec 18, 2024
Primary completion
May 14, 2027 (estimated)
Completion
May 14, 2027 (estimated)
Last update
Nov 5, 2026

Study contacts

Jordan B Branch
Contact
jordan.branch@nih.gov
(301) 221-3820
Swee Lay Thein, M.D.
Contact
sweelay.thein@nih.gov
(301) 435-2345
Swee Lay Thein, M.D.
principal investigator · National Heart, Lung, and Blood Institute (NHLBI)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Fostamatinib

Other studies in this condition

Anemia, Sickle Cell →

Other studies from this sponsor

National Heart, Lung, and Blood Institute (NHLBI) →

Start the discussion