RECRUITING

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

Conditions

Sickle Cell Disease Hb-SS Disease Hemoglobin S Disease Sickle Cell Anemia Sickle Cell Disorders Hemoglobin Beta Thalassemia Disease Sickle Cell Tyrosine Kinase Inhibitor Fostamatinib

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-12-18

Study Completion:2026-05-14

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05904093

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Have provided signed written informed consent 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 hemoglobin 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 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. 2. Absolute neutrophil count \>=1.5 x 10\^9/L. 3. Hemoglobin \>= 7 g/dL 4. Platelet 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 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). 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.	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 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. 5. History of drug-induced cholestatic hepatitis. 6. History of any primary malignancy. 7. 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. 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 investigational or marketed product or placebo. 10. Use of newly approved SCD therapy (L-glutamine, voxelotor 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 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. 14. Currently receiving erythropoiesis stimulating agents.

Inclusion Criteria

Exclusion Criteria

1. Have provided signed written informed consent 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 hemoglobin 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 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.
2. Absolute neutrophil count \>=1.5 x 10\^9/L.
3. Hemoglobin \>= 7 g/dL
4. Platelet 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 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).
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.

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 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.
5. History of drug-induced cholestatic hepatitis.
6. History of any primary malignancy.
7. 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.
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 investigational or marketed product or placebo.
10. Use of newly approved SCD therapy (L-glutamine, voxelotor 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 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.
14. Currently receiving erythropoiesis stimulating agents.

Contacts and Locations

Study Contact

Jordan B Branch

CONTACT

(301) 480-0850

jordan.branch@nih.gov

Swee Lay Thein, M.D.

CONTACT

(301) 435-2345

sweelay.thein@nih.gov

Principal Investigator

Swee Lay Thein, M.D.

PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Swee Lay Thein, M.D., PRINCIPAL_INVESTIGATOR, National Heart, Lung, and Blood Institute (NHLBI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-18

Study Completion Date2026-05-14

Study Record Updates

Study Start Date2024-12-18

Study Completion Date2026-05-14

Terms related to this study

Keywords Provided by Researchers

Sickle Cell
Tyrosine Kinase Inhibitor
Fostamatinib

Additional Relevant MeSH Terms

Sickle Cell Disease
Hb-SS Disease
Hemoglobin S
Disease Sickle Cell Anemia
Sickle Cell Disorders
Hemoglobin Beta Thalassemia Disease