A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease (RISE UP)

Inclusion Criteria: * Age 16 years or older (18 years or older \[France and Germany\]); participants age 16 or 17 years must physically have completed puberty; * Documented diagnosis of sickle cell disease (SCD) (HbSS, HbSC \[combined heterozygosity for hemoglobins S and C\], HbS/beta 0- thalassemia, HbS/ beta plus thalassemia, or other sickle cell syndrome variants); * At least 2 SCPCs and no more than 10 SCPCs in the past 12 months; * Hemoglobin at least 5.5 and 10.5 gram per deciliter (g/dL) at the most. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period; * If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug. Discontinuation of hydroxyurea requires a 90-day washout prior to informed assent/consent; * Women capable of becoming pregnant must agree to use 2 forms of contraception. Exclusion Criteria: * Pregnant, breastfeeding, or parturient; * Receiving regularly scheduled transfusions; * Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease; * Severe kidney disease; * Prior exposure to gene therapy or prior bone marrow or stem cell transplantation; * Currently receiving treatment with a disease-modifying therapy for SCD (eg, voxelotor, crizanlizumab, L-glutamine), with the exception of hydroxyurea. The last dose of voxelotor, crizanlizumab, and L-glutamine must have been administered at least 90 days before randomization; * Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug; * Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial; * Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).