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

Launched by AGIOS PHARMACEUTICALS, INC. · Feb 23, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a medication called mitapivat to see how it affects kidney health in people with sickle cell disease (SCD) who also have nephropathy, which is a condition that affects the kidneys. The main goal is to measure changes in a specific test called the albumin creatinine ratio (ACR), which helps doctors understand how well the kidneys are functioning. The trial is not yet recruiting participants, but when it does, it will be open to individuals aged 16 and older who have a confirmed diagnosis of sickle cell disease and certain kidney health issues.

To be eligible for the trial, participants must have specific hemoglobin levels, which are important for assessing their overall health. They should have stable treatment with hydroxyurea (a medication commonly used for sickle cell disease) or other medications for at least 90 days before joining the study. Participants will be monitored closely and will need to provide urine samples for testing during the study. If you or someone you know is interested in participating, it’s important to discuss this with a healthcare provider to see if they meet the requirements and to learn more about what participation would involve.

Gender

ALL

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;