Vaso oclusive crisis (VOC) is defined as a pain crisis (acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy used to treat VOC. Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study. VOCs included are those HCP-managed in a healthcare facility and HCP-managed via remote consultation. Annualized rate of VOC events = (Number of VOC events \* 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).