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 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.
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 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 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.
3. Has not received fostamatinib in 3 months prior to signing consent