Intro: Sickle cell disease is a genetic disorder caused by a mutation of the β hemoglobin called HbS, which causes red blood cell (RBC) abnormalities responsible for hemolysis, mainly intravascular, leading to chronic anemia. Intravascular hemolysis is responsible for severe inflammation and endothelial dysfunction. Maintaining hemoglobin in its oxygenated R-conformation is one of the strategies for inhibiting the polymerization of HbS. Previous experimental therapeutic approaches having this effect have been discontinued due to poor pharmaceutical properties or toxicity. Nevertheless, they proved the validity of the concept by demonstrating an increase in oxyhemoglobin and a decrease in biomarkers of hemolysis. Voxelotor binds to the α chain of globin and maintains Hb in its R conformation, thereby inhibiting the polymerization of HbS while increasing the affinity of Hb for oxygen. Because of its mechanism of action affecting anemia and hemolysis, Voxelotor is a promising treatment for the prevention and treatment of renal and cerebral arterial disease. Hypothesis/Objective : Investigator hypothesis is that the treatment by Voxelotor (GBT440) will improve intra vascular hemolysis and will increase the total mass of hemoglobin with beneficial effects on organ function. The primary objective of the study is to evaluate the biological activity of Voxelotor on the reduction of intra vascular hemolysis measured by plasma hemoglobin. The secondary objectives of the study will aim at characterizing the effects of GBT 440 Voxelotor on: * Intra vascular hemolysis measured by plasma Heme * Total hemoglobin mass (MHb) * RBCs lifespan * Blood volumes (plasma volume (PV), red blood cell mass (RBCM), total blood volume (BV)) * Blood viscosity * Cerebral perfusion * Cerebrovascular vaso-reactivity * Cognitive function (MoCA) * Six minute walk test * Renal perfusion and iron deposits in renal cortex * Measurement of Glomerular filtration rate Estimation of glomerular filtration rate (CKD/EPI equation) * Urine albumin/creatinine ratio * Ability to decrease or stop erythropoietin in patients under EPO treatment * Safety (VOC, ACS, Priapism) and tolerability of voxelotor * RBC properties Method: This is an open-label, single-arm, single-stage phase II trial in patients treated with Voxelotor 1500 mg daily for 48 weeks. Assessments will be done during the study at week 0, week 6, week 12, week 24, week 36 and week 48.