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

The primary purpose of this study is to evaluate the effect of mitapivat on albumin creatinine ratio (ACR) response in participants with sickle cell disease (SCD) and nephropathy.


Eligibility Criteria:
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;