A Study of Tebapivat (AG-946) in Participants With Anemia Due to Lower-Risk Myelodysplastic Syndromes (LR-MDS)

Running, not enrolling · Phase 2

Conditions studied: Myelodysplastic Syndromes

In brief

This purpose of this study is to establish proof of concept of tebapivat in participants with LR-MDS in Phase 2a and to evaluate the effect of tebapivat on transfusion independence (TI) in participants with LR-MDS in phase 2b.

Key facts

Study ID

NCT05490446

Run by

Agios Pharmaceuticals, Inc.

People needed

87

Starts

2022-11-07

Expected to finish

2029-03-01

Last updated by the study team

2026-07-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Phase 2a
• At least 18 years of age at the time of providing informed consent;
• Documented diagnosis of myelodysplastic syndromes (MDS) according to World Health Organization (WHO) classification (Arber et al, 2016), that meets Revised International Prognostic Scoring System (IPSS-R) classification of lower-risk disease (risk score: ≤3.5) and <5% blasts as determined by the participant's bone marrow biopsy/aspirate during the Screening Period;
• Nontransfused or with low transfusion burden (LTB), based on transfusion history from the participant's medical record, according to revised International Working Group (IWG) 2018 criteria:
• Nontransfused (NTD): <3 red blood cell (RBC) units in the 16-week period before administration of the first dose of study drug and no transfusions in the 8-week period before administration of the first dose of study drug, or
• LTB: 3 to 7 RBC units in the 16-week period before administration of the first dose of study drug and <4 RBC units in the 8-week period before administration of the first dose of study drug;
• A hemoglobin (Hb) concentration <11.0 grams per deciliter (g/dL) during the 4-week Screening Period;
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2;
• If taking iron chelation therapy, the iron chelation therapy dose must have been stable and started ≥56 days before administration of the first dose of study drug;
• Women of childbearing potential (WOCBP) must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a highly effective method of contraception from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug; if the highly effective method of contraception is hormonal contraception, then an acceptable barrier method must also be used. Men with partners who are WOCBP must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a condom from the time of providing informed consent throughout the study and for 28 days after the last dose of study drug;
• Written informed consent from the participant before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.
• Phase 2b
• At least 18 years of age at the time of providing informed consent;
• Documented diagnosis of MDS according to WHO classification (Arber et al, 2016), that meets IPSS-R classification of lower-risk disease (risk score: ≤3.5) and <5% blasts as determined by the participant's bone marrow biopsy/aspirate during the Screening Period;
• With LTB, or high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria:
• LTB: 3 to 7 RBC units from at least 2 transfusion episodes in the 16-week period before administration of the first dose of study drug AND <4 RBC units in the 8-week period before administration of the first dose of study drug, or
• HTB: ≥8 RBC units in the 16-week period before administration of the first dose of study drug AND ≥4 RBC units in the 8-week period before administration of the first dose of study drug
• If a participant's transfusion burden does not fall into either the LTB or HTB category, as defined per IWG 2018 criteria, then the transfusion burden will be categorized based on their transfusion history in the 16-week period before administration of the first dose of study drug.
• Pretransfusion Hb concentration available for a minimum of 2 and at least half (50%) of the transfusions received in the 16-week period before administration of the first dose of study drug
• A Hb concentration <10.0 g/dL during the 4-week Screening Period;
• Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin [EPO], EPO + granulocyte colony-stimulating factor [G-CSF]) and/or luspatercept;
• ECOG Performance Status score of 0, 1, or 2;
• If taking iron chelation therapy, the iron chelation therapy dose must have been stable and started ≥56 days before administration of the first dose of study drug;
• WOCBP must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a highly effective, from the time of providing informed consent throughout the study and for 28 days after the last dose of study drug; if the highly effective method of contraception is hormonal contraception, then an acceptable barrier method must be used. Men with partners who are WOCBP must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use a condom from the time of providing informed consent throughout the study and for 28 days after the last dose of study drug;
• Written informed consent from the participant before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.

You may not qualify if…

• Phase 2a
• Known history of acute myeloid leukemia (AML);
• Secondary MDS, defined as MDS that is known to have arisen as a result of chemical injury or treatment with chemotherapy and/or radiation for other diseases;
• Prior exposure to a pyruvate kinase activator and/or disease-modifying agents for underlying MDS:
• Immunomodulatory drugs (IMiDs) such as lenalidomide; at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤1 week of treatment with IMiDs may not be excluded, provided their last dose was ≥8 weeks before administration of the first dose of study drug
• Hypomethylating agents (HMAs); at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤2 doses of HMAs may not be excluded, provided that their last dose was ≥8 weeks before administration of the first dose of study drug
• Isocitrate dehydrogenase (IDH) inhibitors
• Immunosuppressive therapy (IST)
• Allogeneic or autologous stem cell transplant;
• Currently receiving treatment with ESAs±G-CSF and/or luspatercept. Treatment with ESAs±G-CSF must have been stopped for ≥28 days before administration of the first dose of study drug; treatment with luspatercept must have been stopped for ≥65 days before administration of the first dose of study drug;
• History of active and/or uncontrolled cardiac or pulmonary disease within 6 months before providing informed consent, including but not limited to:
• New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia
• Myocardial infarction, unstable angina pectoris, or unstable hypertension; high risk thrombosis; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism
• Heart rate-corrected QT interval using Fridericia's method of ≥470 milliseconds for female participants and ≥450 milliseconds for male participants, except for right or left bundle branch block
• Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis >50%
• Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right-sided heart failure, and oxygen indicated;
• History of hepatobiliary disorders, as defined by:
• Serum aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN) (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase (ALT) >2.5 × ULN (unless due to hepatic iron deposition)
• Serum bilirubin >ULN, if the elevation is associated with clinically symptomatic choledocholithiasis, cholecystitis, biliary obstruction, or hepatocellular disease;
• Renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) <45 milliliters per minute (mL/min)/1.73 m\^2;
• Active infection requiring systemic antimicrobial therapy at the time of providing informed consent. If antimicrobial therapy is required during the Screening Period, screening procedures should not be performed while antimicrobial therapy is being administered, and the last dose of antimicrobial therapy must be administered ≥7 days before administration of the first dose of study drug;
• Major surgery within 12 weeks before administration of the first dose of study drug. Participants must have completely recovered from any previous surgery before administration of the first dose of study drug;
• For any malignancy except MDS: History of malignancy (active or treated) ≤5 years before providing informed consent for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;
• Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);
• Positive test for HIV-1 Ab or HIV-2 Ab;

Where it is running

• Innovative Clinical Research Institute Whittier — Lakewood, California, United States
• David Geffen School of Medicine at UCLA — Los Angeles, California, United States
• Emad Ibrahim, MD, Inc. — Redlands, California, United States
• Smilow Cancer Hospital at Yale New Haven — New Haven, Connecticut, United States
• Mayo Clinic Jacksonville - PPDS — Jacksonville, Florida, United States
• Edward H. Kaplan MD & Associates — Skokie, Illinois, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Memorial Sloan Kettering Cancer Center — Long Island City, New York, United States
• Duke Adult Blood and Marrow Clinic — Durham, North Carolina, United States
• Monash Health, Monash Medical Centre — Clayton, Victoria, Australia
• Ordensklinikum Linz GmbH Elisabethinen — Linz, Upper Austria, Austria
• Fakultni nemocnice Ostrava — Ostrava, Czechia
• Hôpital de La Conception — Marseille, Bouches-du-Rhône, France
• CHU Angers — Angers, Maine-et-Loire, France
• CHRU Lille — Lille, France
• Hôpital Saint Louis — Paris, France
• Medizinische Hochschule Hannover — Hanover, Lower Saxony, Germany
• Universitatsklinikum Dusseldorf — Düsseldorf, North Rhine-Westphalia, Germany
• Universitatsklinikum Leipzig — Leipzig, Saxony, Germany
• University Hospital of Alexandroupolis — Alexandroupoli, Greece
• Attikon University General Hospital — Athens, Greece
• University General Hospital of Patras — Pátrai, Greece
• Hippokration Hospital — Thessaloniki, Greece
• Shaare Zedek Medical Center — Jerusalem, Israel
• Tel Aviv Sourasky Medical Center PPDS — Tel Aviv, Israel

Full record on ClinicalTrials.gov

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