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Researchers are evaluating how well etavopivat works to reduce the number of vaso-occlusive crises (painful blood vessel blockages) in adolescents and adults living with sickle cell disease. The study also aims to assess if etavopivat can decrease organ damage, improve exercise tolerance, and reduce fatigue. This is a global Phase 3 study involving participants aged 12 years and older with confirmed sickle cell disease. The study is randomized, double-blind, and placebo-controlled to ensure accurate evaluation of the treatment effects. Participants will receive either etavopivat or a matching placebo by mouth. Which treatment they receive is determined randomly. The study will last about two years, during which participants will take the assigned medication and be monitored closely. Etavopivat is an investigational drug currently under evaluation in multiple studies for sickle cell disease. During the study, participants will have regular assessments including documentation of vaso-occlusive crisis events, blood tests, and physical evaluations. Researchers will track the number of crises that require medical attention over a 52-week period, as well as measures of organ health, exercise ability, and fatigue. Safety and overall health will be monitored throughout the study, with the total participation time lasting approximately two years.