Actigraphy Improvement With Voxelotor (ActIVe) Study

Exclusion Criteria

• •1. Red blood cell (RBC transfusion within 3 months before initiation of study drug
• •2. Planned initiation of regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study
• •3. Hospitalization for vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) within 30 days prior to informed consent/assent.
• •4. More than 10 VOCs requiring hospitalization, emergency department or clinic visit within the past 12 months
• •5. Planned elective surgery within the next 6 months
• •6. Physical inactivity attributable to clinically significant musculoskeletal, cardiovascular, or respiratory comorbidities
• •7. Anemia due to bone marrow failure (eg, myelodysplasia)
• •8. Absolute reticulocyte count (ARC) \< 100 x10\^9/L
• •9. Screening alanine aminotransferase (ALT) \> 4× upper limit of normal (ULN)
• •10. Severe renal dysfunction (estimated glomerular filtration rate \[GFR\] \< 30 mL/min/1.73 m2 by Schwartz formula) or is on chronic dialysis
• •11. Known active hepatitis A, B or C or known to be human immunodeficiency virus (HIV)-positive.
• •12. Females who are breast-feeding or pregnant
• •13. Major surgery within 8 weeks before enrollment. Participants must have completely recovered from any previous surgery before enrollment
• •14. History of hematopoietic stem cell transplant or gene therapy
• •15. Received an investigational drug within 30 days or 5-half-lives, whichever is longer, prior to consent, or is currently participating in another trial of an investigational or marketed drug (or medical device)
• •16. Use of concomitant medications (eg, crizanlizumab) that confound the ability to interpret data from the study
• •17. 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
• •18. Use of herbal medications (e.g., St. John's Wort), sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or moderate or strong CYP3A4 inducers
• •19. Symptomatic coronavirus disease of 2019 (COVID-19) infection