a study of mitapivat in participants with sickle cell disease and nephropathy

Conditions: Sickle Cell Disease; Nephropathy

Summary: 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;

Keywords: ag-348 mitapivat