A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia

NCT ID: NCT03692052

Last Updated: 2026-01-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2030-09-30

Brief Summary

Study AG348-C-010 is a multicenter study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of treatment with AG-348 in adult participants with non-transfusion-dependent thalassemia (NTDT). This study includes a core period (up to 24 weeks) followed by an extension period (up to 10 years) for eligible participants. 20 participants with NTDT were enrolled. The initial dose of AG-348 was 50 milligrams (mg) twice daily (BID) with one potential dose-level increase to 100 mg BID at the Week 6 visit based on the participant's safety and hemoglobin (Hb) concentrations.

Conditions

Thalassemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AG-348

Participants with alpha or beta thalassemia received AG-348 50 mg twice daily (BID), orally up to Week 6. Following Week 6, depending on the participants' safety and hemoglobin (Hb) concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.

Group Type: EXPERIMENTAL

AG-348

Intervention Type: DRUG

AG-348 tablet orally BID

Interventions

AG-348

AG-348 tablet orally BID

Intervention Type: DRUG

Other Intervention Names

Mitapivat

Eligibility Criteria

Inclusion Criteria

• Informed consent;
• Known medical history of thalassemia, including β-thalassemia intermedia, Hb E β-thalassemia, α-thalassemia (Hb H disease), or β-thalassemia with mutations of 1 or more α genes;
• Documented clinical laboratory confirmation of thalassemia by Hb electrophoresis/high-performance liquid chromatography (HPLC) or deoxyribonucleic acid (DNA) analysis, either from medical records or during the screening period;
• Hb concentration ≤10.0 grams per deciliter (g/dL), regardless of sex, based on an average of at least 2 Hb measurements (separated by a minimum of 7 days) during the screening period;
• Considered non-transfusion-dependent, defined as having no more than 5 units of red blood cells (RBCs) transfused during the 24-week period up to the first day of study drug and no RBC transfusions in the 8 weeks prior to the first day of study drug;
• Adequate organ function;
• For women of reproductive potential: negative serum pregnancy test during the screening period and a negative serum or urine pregnancy test on Day 1;
• For women of reproductive potential as well as men with partners who are women of reproductive potential: be abstinent as part of their usual lifestyle, or agreement to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men;
• Willingness to comply with all study procedures for the duration of the study;

Exclusion Criteria

• Known history of diagnosis of Hb S or Hb C forms of thalassemia;
• Significant medical condition that confers an unacceptable risk to participating in the study, and/or could confound the interpretation of the study data;
• Splenectomy scheduled during the study treatment period or having undergone splenectomy within 12 months prior to signing informed consent;
• Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo;
• Exposure to any investigational drug, device, or procedure within 3 months prior to the first day of study drug;
• Prior exposure to sotatercept (ACE-011), luspatercept (ACE-536), ruxolitinib, or gene therapy;
• Prior bone marrow or stem cell transplant;
• Currently pregnant or breastfeeding;
• History of major surgery within 6 months of signing informed consent;
• Currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first day of study drug;
• Currently receiving chronic anticoagulant therapy, unless started and on a stable dose for at least 28 days prior to first day of study drug;
• Currently receiving anabolic steroids, including testosterone preparations, if initiated ≤28 days prior to the first day of study drug;
• Currently receiving hematopoietic stimulating agents (e.g., erythropoietins, granulocyte colony stimulating factors, thrombopoietins), if initiated ≤8 weeks prior to the first day of study drug;
• History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug-induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis, or other serious clinical manifestations;
• History of allergy to AG-348 or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, and mannitol).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Affairs

Role: STUDY_CHAIR

Agios Pharmaceuticals, Inc.

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University Health Network (Toronto General Hospital)

Toronto, Ontario, Canada

Imperial College Healthcare NHS Trust (Hammersmith Hospital)

London, , United Kingdom

Countries

United States; Canada; United Kingdom

References

Kuo KHM, Layton DM, Lal A, Al-Samkari H, Bhatia J, Kosinski PA, Tong B, Lynch M, Uhlig K, Vichinsky EP. Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent alpha-thalassaemia or beta-thalassaemia: an open-label, multicentre, phase 2 study. Lancet. 2022 Aug 13;400(10351):493-501. doi: 10.1016/S0140-6736(22)01337-X.

Reference Type: DERIVED

PMID: 35964609 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002217-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AG348-C-010

Identifier Type: -

Identifier Source: org_study_id