A Study of Mitapivat in Participants With Sickle Cell Disease and Nephropathy

Key Inclusion Criteria: * Age of 16 years or older (except in France where participants must be aged 18 years or older); * Females must be post-menarche; * Documented diagnosis of sickle cell disease (Homozygosity for hemoglobin S \[HbSS\] or Hemoglobin S/Beta 0 \[HbS/β0\]-thalassemia); * Hemoglobin concentration ≥ 5.5 and ≤ 10.5 grams per deciliter (g/dL) during the Screening Period. If more than one measurement is collected during the Screening Period, the average must be ≥ 5.5 and ≤ 10.5 g/dL; * If taking hydroxyurea, the dose of hydroxyurea must have been stable for at least 90 days before Study Day 1 with no planned dose adjustment during the study and no sign of hematologic toxicity; * Discontinuation of hydroxyurea requires a 90-day washout before providing informed consent/assent; * Two urine ACR results collected during the Screening Period, both of which must be ≥ 100 and \< 2000 milligrams per gram (mg/g). One ACR result can be from an untimed urine sample collected as part of a clinic visit. The other ACR result must be from a urine sample that is the first (or second) morning void on another day; * One ACR result \> 100 mg/g within 24 weeks before providing informed consent/assent; * If taking Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin receptor blockers (ARB) therapy, must have been on stable dose for at least 90 days before providing informed consent/assent with no planned dose adjustment during the study; * Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, one of which must be considered highly effective, from the time of providing informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method. Key Exclusion Criteria: * Pregnant, breastfeeding, or parturient; * Currently receiving regularly scheduled red RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted; * Have received an RBC transfusion within 60 days before providing informed consent/assent or during the Screening Period; * Hospitalized within 14 days before providing informed consent/assent or during the Screening Period either for a sickle cell disease pain crisis (SCPC) or other vaso-occlusive event; * More than 10 SCPCs in the 52 weeks before providing informed consent/assent; * History of stroke or meeting criteria for primary stroke prophylaxis (history of 2 transcranial Doppler \[TCD\] measurements ≥ 200 centimeters per second (cm/s) by nonimaging TCD or ≥ 185 cm/s by imaging TCD) at any time; * Renal dysfunction as defined by an eGFR \< 45 milliliters per minute (mL/min)/1.73 meters per square (m\^2) by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (National Kidney Foundation, 2021b) at Screening; * History of renal disease due to another disorder (e.g., diabetes, hypertension, primary focal segmental glomerulosclerosis, autoimmune) unrelated to SCD at any time; * Evidence of acute kidney injury (in the opinion of the Investigator) within 4 weeks before informed consent/assent or during Screening Period. * Currently undergoing renal replacement therapy (i.e., hemodialysis, peritoneal dialysis, hemofiltration, kidney transplantation); * History of kidney transplant at any time; * Currently receiving treatment with a disease-modifying therapy for SCD (eg, voxelotor, crizanlizumab, L-glutamine), except for hydroxyurea. The last dose of such therapies must have been administered at least 90 days before starting study drug; * Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug;