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

NCT03692052 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: AG348-C-0102018-002217-35
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 4

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving a Hemoglobin Response (HR)

  HR was defined as a ≥1.0 gram per deciliter (g/dL) increase in Hb concentration from Baseline at 1 or more assessments between Week 4 and Week 12 (inclusive). A participant's Baseline Hb concentration was defined as the average of all the participant's available Hb concentrations during the screening period up to the first dose of study drug.

  Up to 12 weeks

Secondary Outcomes (20)

• Average Change From Baseline in Hb Concentrations From Week 12 to Week 24

  Baseline, Week 12 to Week 24

• Percentage of Participants Achieving a Sustained Hb Response (sHR)

  Week 12 to Week 24

• Percentage of Participants Achieving a Delayed Hb Response

  Week 12 to Week 24

• Change From Baseline in Hb Concentration Over the Duration of the Extension Period

  Baseline up to approximately 10.5 years

• Time to First ≥1.0 g/dL Increase in Hb Concentration

  Up to Week 24

Study Arms (1)

AG-348

EXPERIMENTAL

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.

Drug: AG-348

Interventions

AG-348 DRUG

AG-348 tablet orally BID

Also known as: Mitapivat

AG-348

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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).

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (4)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University Health Network (Toronto General Hospital)

Toronto, Ontario, M5G 2C4, Canada

Location

Imperial College Healthcare NHS Trust (Hammersmith Hospital)

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35964609 DERIVED

MeSH Terms

Conditions

Thalassemia

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

Results Point of Contact

• Title: Medical Affairs
• Organization: Agios Pharmaceuticals, Inc.

medinfo@agios.com

833-228-8474

Study Officials

• Medical Affairs

  Agios Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: September 10, 2018
• First Posted: October 2, 2018
• Study Start: March 20, 2019
• Primary Completion: August 20, 2020
• Study Completion (Estimated): September 30, 2030
• Last Updated: March 30, 2026
• Results First Posted: November 15, 2021

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); GB (1); US (2)