Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA

Eligibility Criteria

• 1. Adult participants age 16 and older
• 2. Sickle cell disease with confirmation of HbSS, HbSBthal0, HbSC, or HbS thal+ genotype
• 3. Per patient's sickle cell provider, patient has an increased risk of a silent cerebral infarcts according to one of the following criteria:
• 1. Silent cerebral infarcts visualized on FLAIR MRI within previous two years
• 2. Intracranial or extracranial cervical artery vasculopathy
• 3. History of overt ischemic or hemorrhagic stroke and Intolerance and/or failure of other therapies to prevent cerebral infarction
• 4. Increased severity of sickle cell disease including having between 2 and 10 sickle cell-related pain crises within the preceding 12 months as determined by medical history or by patient's recall (crises should include the occurrence of appropriate symptoms, a visit to a specific medical facility and/or health care professional, and receipt of pain medication).
• 5. Increased risk deemed by other objective laboratory and/or imaging results which have been associated with increased risk of cerebral infarction
• 4. Provide written informed consent.
• 5. Normal hematologic function defined as: WBC \> 4x10\^9 / L, ANC \>1.5x10\^9 / L and platelets \> 100x10\^9 / L
• 6. Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on crizanlizumb and for 3 months after discontinuation from crizanlizumab, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc.), barrier method contraception (i.e. condoms), or abstinence during the time-frame
• 1. Current chronic transfusion therapy
• 2. Planning for hematopoietic stem cell transplant or cerebral revascularization procedure
• 3. Use of other investigational drug within one year of study participation
• 4. Other medical/neurological/social/substance abuse history that would alter brain MRI findings prospectively
• 5. Inability to return for follow-up
• 6. Contraindication to MRI
• 7. Acute bacterial, fungal, or viral infection
• 8. Known HIV, untreated latent tuberculosis (TB), or active hepatitis B or C infection or zoster
• 9. Pregnant and/or breastfeeding. Negative pregnancy test required prior to starting study treatment.
• 10. Known hypersensitivity to one or more of the study agents
• 11. Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
• 12. Liver function tests (LFT) higher than 3x the upper limit of normal
• 13. Treatment with other monoclonal antibody medications within last 30 days
• 14. Treatment with various forms of anticoagulation within last 30 days, including but not limited to coumadin or direct thrombin inhibitors