Voxelotor Brain Oxygenation and Neurocognitive Study

Inclusion Criteria: 1. Male or female participants with confirmed diagnosis of SCD with HbSS or Hbβ0 thalassemia genotype. Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening. 2. Aged 12 to 30 years. 3. Screening Hb level ≥ 5.5 and ≤ 10.5 g/dL. 4. Must meet site-specific compliance requirements for a diagnostic MRI scan. 5. Able to answer NIH Toolbox Module questions in English 6. If participant is receiving hydroxyurea (HU) they must have been on a stable dose for at least 90 days prior to signing the ICF/AF, with no dose modifications or initiation of HU planned or anticipated by the Investigator. 7. If participant is receiving erythropoiesis-stimulating agents (ESAs) they must have been on a stable dose for at least 12 weeks before enrollment with no dose modifications planned or anticipated by the Investigator. 8. Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception from study start to 30 days after the last dose of study drug and who if male, agree to use barrier methods of contraception and refrain from donating sperm from study start to 30 days after the last dose of study drug. 9. Females of child-bearing potential must have a negative pregnancy test before the administration of study drug. 10. Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12-17 years) per Institutional Review Board (IRB) policy and requirements, consistent with ICH guidelines. 11. Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study. Exclusion Criteria: 1. History of overt stroke including hemorrhagic stroke, transient ischemic attacks, or spinal cord injury. 2. Grade 4 vasculopathy defined as moderate stenosis (50% to 69%) in more than 2 major cerebral arteries or severe stenosis (\> 70%) in any major cerebral artery. 3. Non-MRI compatible metal hardware and/or metal braces. 4. Congenital brain malformation, previously diagnosed severe developmental disability (eg autism and/or intelligence quotient \[IQ\] \<60, and/or severe attention deficit hyperactivity disorder \[ADHD\]), or impairment that would prevent the use of a computer tablet. 5. Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit. 6. Participant is taking or has received crizanlizumab (Adakveo®) within 90 days prior to the Screening Visit. 7. Vaso-occlusive event requiring intravenous opioids within 28 days prior to Day 1. 8. Red blood cell (RBC) transfusion within 3 months before initiation of study drug or receives scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion). 9. Surgery within 8 weeks before Day 1 or planned elective surgery during the study. 10. Anemia due to bone marrow failure (eg, myelodysplasia). 11. Absolute reticulocyte count (ARC) \< 100 × 10\^9/L. 12. Screening alanine aminotransferase or aspartate aminotransferase \> 4× upper limit of normal (ULN). 13. Severe renal dysfunction (estimated glomerular filtration rate \[eGFR\] \<45 mL/min/1.73 m\^2) or on chronic dialysis. 14. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy 1. Acute bacterial infection requiring antibiotic use should delay Screening/enrollment until the course of antibiotic therapy has been completed. 2. Known active hepatitis A, B, or C or are known to be human immunodeficiency virus (HIV) positive. 15. Symptomatic coronavirus disease of 2019 (COVID-19) infection. 16. Females who are breast-feeding or pregnant. 17. History of hematopoietic stem cell transplant or gene therapy. 18. Participants taking concomitant medications such as sensitive CYP3A4 substrates with a narrow therapeutic range, or strong CYP3A4 inducers. 19. Participated in another clinical trial of an investigational product (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational product (or medical device). 20. Medical, psychological, or behavioral condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or efficacy of the study drug, prevent compliance with the study protocol; preclude informed consent; or render the participant unable/unlikely to comply with the study procedures (particularly the MRI scan).