A Dose-Finding Study of AG-348 in Sickle Cell Disease

Summary

Background: Sickle Cell Disease (SCD) is an inherited blood disorder. People with SCD have abnormal hemoglobin in their red blood cells. Researchers are investigating the safety and efficacy of an investigational medicine called AG-348 (mitapivat sulfate) to determine if it will help people with SCD. Objective: To test the tolerability and safety of AG-348 in people with SCD. Eligibility: People ages 18 and older with SCD. Design: Participants will have 8 visits over approximately 14 weeks. At the first visit participants will be screened with a medical history, a physical exam, blood and urine testing, and an EKG. During the following 5 visits, participants will stay at the clinic for 1 night each. Participants will take study drug in increasing doses up to visit 6, after which the drug will be tapered off. All visits will include physical exam, blood, and urine tests. The last visit will occur 4 weeks after stopping the drug. Participants will provide DNA from the blood samples they provide. The DNA will be tested for an inherited gene that can cause differences in response to the study drug. Researchers may also test other genes to see if they can find any genes that interact with SCD.

Timeline

Start

2019-07-11

Primary completion

2021-06-21

Completion

2021-06-21

Publications

• Conrey A, Asomaning N, Frey I, Charles RP, Lovins D, Xu JZ, Mendez-Marti S, Le K, Kruah B, Li Q, Dunkelberger E, Cellmer T, Yates A, Wind-Rotolo M, Huston C, Jeffries N, Eaton WA, Thein SL. Long-term mitapivat treatment is safe and efficacious in patients with sickle cell disease. Blood Red Cells Iron. 2025 Sep;1(2):100014. doi: 10.1016/j.brci.2025.100014. Epub 2025 Sep 11.
• Le K, Wang X, Chu J, Lundt M, Lee YY, Conrey A, Frey I, Giannini S, Kosinski PA, Hausman JM, Low PS, Jeffries N, Desai SA, Thein SL. Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation. Blood Adv. 2024 Nov 12;8(21):5653-5662. doi: 10.1182/bloodadvances.2024013504.
• Xu JZ, Conrey A, Frey I, Gwaabe E, Menapace LA, Tumburu L, Lundt M, Lequang T, Li Q, Glass K, Dunkelberger EB, Iyer V, Mangus H, Kung C, Dang L, Kosinski PA, Hawkins P, Jeffries N, Eaton WA, Lay Thein S. A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease. Blood. 2022 Nov 10;140(19):2053-2062. doi: 10.1182/blood.2022015403.

Drugs

Indications