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

NCT06286046 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: AG348-C-0262023-510289-28-00
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Sickle Cell Disease; Nephropathy

Keywords

AG-348; Mitapivat

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Albumin Creatinine Ratio (ACR) Response

  The ACR response is defined as a decrease of 30% or more in ACR from the baseline to Month 6.

  Baseline up to 6 months

Secondary Outcomes (6)

• Change From Baseline in Cystatin C and Creatinine-based Estimated Glomerular Filtration Rate (eGFRcr-cys)

  Baseline up to 25 months

• Change From Baseline in Albumin Creatinine Ratio (ACR)

  Baseline up to 25 months

• Percentage of Participants With Stable ACR

  Baseline up to 6 months

• Annualized Rate of Emergency Room (ER) Visits

  Up to 24 months

• Annualized Rate of Days of Hospitalizations

  Up to 24 months

Study Arms (1)

Mitapivat 100 mg

EXPERIMENTAL

Participants will receive mitapivat 100 milligrams (mg) tablet, orally, twice daily (BID) for up to 24 months.

Drug: Mitapivat

Interventions

Mitapivat DRUG

Tablets

Also known as: AG-348, Mitapivat sulfate, AG-348 sulfate hydrate

Mitapivat 100 mg

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Related Publications (1)

• Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.

  PMID: 40569673 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Kidney Diseases

Interventions

mitapivat

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Agios Medical Affairs

CONTACT

833-228-8474; medinfo@agios.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: February 29, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share