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AzTrials

Myelodysplastic SyndromesPhase 2NCT05490446

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

A Phase 2 study testing Tebapivat in people with Myelodysplastic Syndromes, run by Agios Pharmaceuticals, Inc. at 45 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Tebapivat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
45 sitesin 13 countries
Study dates
7 Nov 2022to Mar 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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
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  • 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;
  • Absolute neutrophil count (ANC) <500/microliter (μL) (0.5 × 10^9/L);
  • Platelet count ≤75,000/μL during Screening (75 × 10^9/L) platelet transfusions within 28 days before Screening or during Screening;
  • Nonfasting triglyceride concentration >500 mg/dL;
  • Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug;
  • Current enrollment or past participation (within 4 weeks or a time frame equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug or, whichever is longer) in any other clinical study involving an investigational treatment or device;
  • Known allergy to tebapivat or its excipients;
  • Pregnant or breastfeeding;
  • Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
  • Participants who are institutionalized by regulatory or court order;
  • Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).
  • Phase 2b
  • Known history of 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, including exposure to tebapivat in the Phase 2a part of this study, and/or disease-modifying agents for underlying MDS:
  • Imetelstat; at the Investigator's discretion and in consultation with the Medical Monitor, participants who received ≤2 doses of imetelstat may not be excluded, provided that their last dose was ≥8 weeks before administration of the first dose of study drug
  • 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
  • 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
  • IDH inhibitors
  • 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 AST >2.5 × ULN (unless due to hemolysis and/or hepatic iron deposition) and 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 eGFR <45 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, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ.;
  • Positive test for HCV Ab with evidence of active HCV infection, or positive test for HBsAg;
  • Positive test for HIV-1 Ab or HIV-2 Ab;
  • ANC <500/μL (0.5 × 10^9/L);
  • Platelet count < 75,000/μL (75 × 10^9 /L) during Screening; platelet transfusions within 28 days before Screening or during Screening;
  • Nonfasting triglyceride concentration >500 mg/dL;
  • Receiving inhibitors of P-gp that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer) beforeadministration of the first dose of study drug;
  • Current enrollment or past participation (within 4 weeks or a time frame equivalent to 5 half-lives of the investigational study drug before administration of the first dose of study drug or, whichever is longer) in any other clinical study involving an investigational treatment or device;
  • Known allergy to tebapivat or its excipients;
  • Pregnant or breastfeeding;
  • Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
  • Participants who are institutionalized by regulatory or court order
  • Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor).
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, autoimmune or hereditary hemolytic anemia, hypothyroidism, or any type of known clinically significant bleeding.

Trial locations and contacts

45 sites in 13 countries.

45 sites in 13 countries

United States9 sites

  • Duke Adult Blood and Marrow Clinic

    Durham, North Carolina, 27705

  • Mayo Clinic Jacksonville - PPDS

    Jacksonville, Florida, 32224

  • Innovative Clinical Research Institute Whittier

    Lakewood, California, 90805

  • Memorial Sloan Kettering Cancer Center

    Long Island City, New York, 11101

  • David Geffen School of Medicine at UCLA

    Los Angeles, California, 90024

  • Smilow Cancer Hospital at Yale New Haven

    New Haven, Connecticut, 06510

  • Emad Ibrahim, MD, Inc.

    Redlands, California, 92373

  • Edward H. Kaplan MD & Associates

    Skokie, Illinois, 60076

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Italy5 sites

  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

    Milan, Lombardy

  • Fondazione IRCCS Policlinico San Matteo di Pavia

    Pavia, Lombardy

  • Fondazione PTV Policlinico Tor Vergata

    Roma

  • Istituto Clinico Humanitas

    Rozzano, Lombardy

  • Azienda Ospedaliera Ordine Mauriziano di Torino

    Turin, Piedmont

Other trials in Italy

Spain5 sites

  • C.H. Regional Reina Sofia - PPDS

    Córdoba, 14004

  • Hospital Universitario La Paz - PPDS

    Madrid, 28046

  • Hospital Universitario HM Sanchinarro - CIOCC

    Madrid, 28050

  • Complejo Asistencial Universitario de Salamanca - H. Clinico

    Salamanca, 37007

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

Other trials in Spain

France4 sites

  • CHU Angers

    Angers, Maine-et-Loire, 49933

  • CHRU Lille

    Lille, 59037

  • Hôpital de La Conception

    Marseille, Bouches-du-Rhône, 13010

  • Hôpital Saint Louis

    Paris, 75475

Other trials in France

Greece4 sites

  • University Hospital of Alexandroupolis

    Alexandroupoli

  • Attikon University General Hospital

    Athens

  • University General Hospital of Patras

    Pátrai

  • Hippokration Hospital

    Thessaloniki

Other trials in Greece

United Kingdom4 sites

  • Aberdeen Royal Infirmary - PPDS

    Aberdeen, Aberdeen City, AB25 2ZN

  • Western General Hospital Edinburgh - PPDS

    Edinburgh, EH24 2XU

  • Kings College Hospital

    London, SE5 9RS

  • Churchill Hospital-NHS Oxford

    Oxford, OX3 7LE

Other trials in United Kingdom

Germany3 sites

  • Universitatsklinikum Dusseldorf

    Düsseldorf, North Rhine-Westphalia, 40225

  • Medizinische Hochschule Hannover

    Hanover, Lower Saxony, 30625

  • Universitatsklinikum Leipzig

    Leipzig, Saxony, 04103

Other trials in Germany

Poland3 sites

  • Pratia Onkologia Katowice - PRATIA - PPDS

    Katowice, Silesian Voivodeship

  • SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

    Olsztyn, Warmian-Masurian Voivodeship

  • MTZ Clinical Research Powered by PRATIA - PPDS

    Warsaw, Masovian Voivodeship

Other trials in Poland

South Korea3 sites

  • Kyungpook National University Hospital

    Daegu, 41944

  • Asan Medical Center - PPDS

    Seoul, 05505

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul

Other trials in South Korea

Israel2 sites

  • Shaare Zedek Medical Center

    Jerusalem, 9103102

  • Tel Aviv Sourasky Medical Center PPDS

    Tel Aviv

Other trials in Israel

Australia1 site

  • Monash Health, Monash Medical Centre

    Clayton, Victoria, 3168

Other trials in Australia

Austria1 site

  • Ordensklinikum Linz GmbH Elisabethinen

    Linz, Upper Austria, 4020

Other trials in Austria

Czechia1 site

  • Fakultni nemocnice Ostrava

    Ostrava, 708 52

Other trials in Czechia

About this study

Official title: A Phase 2a/2b, Open-label, Proof of Concept (Phase 2a) and Open-label (Phase 2b), Multicenter, Efficacy, and Safety Study of AG-946 in Participants With Anemia Due to Lower-Risk Myelodysplastic Syndromes

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.

Being tested
Tebapivat
Keywords
Anemia, Lower-Risk Myelodysplastic Syndromes
Medical subject headings
Myelodysplastic Syndromes, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TebapivatDrug

    Also called AG-946

    Tebapivat Tablet

Study groups in NCT05490446
Study groupRoleWhat they receive
Core Period: Phase 2a - Tebapivat 5 mgExperimentalParticipants will receive 5 milligrams (mg) tebapivat orally, once daily for up to 16 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.
Receives: Drug: Tebapivat
Core Period: Phase 2b - Tebapivat 10 mgExperimentalParticipants will receive 10 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.
Receives: Drug: Tebapivat
Core Period: Phase 2b - Tebapivat 15 mgExperimentalParticipants will receive 15 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.
Receives: Drug: Tebapivat
Core Period: Phase 2b - Tebapivat 20 mgExperimentalParticipants will receive 20 mg tebapivat, orally, once daily for up to 24 weeks. At the discretion of the investigator, participants who complete the Core Period will be eligible to receive the same dose in Extension Period for up to 156 weeks.
Receives: Drug: Tebapivat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 2a: Proportion of Participants With Hemoglobin (Hb) Response

    Hb response is defined as a ≥1.5-grams per deciliter (g/dL) increase from baseline in the average Hb concentration from Week 8 through Week 16.

    Measured: Baseline, Week 8 through Week 16

  2. Phase 2a: Proportion of Participants With Transfusion Independence During the Core Period

    Transfusion Independence is defined as transfusion-free for ≥8 consecutive weeks during the Core Period (participants With Low Transfusion Burden [LTB] only).

    Measured: Up to 16 weeks

  3. Phase 2b: Proportion of Participants With Transfusion Independence

    Transfusion independence, defined as transfusion-free for ≥8 consecutive weeks (TI8) during the Core Period.

    Measured: Up to 24 weeks

Secondary outcomes (33)

  1. Phase 2a: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period

    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any AE or suspected adverse reaction that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly/birth defect, or is considered an important medical event.

    Measured: Up to 16 weeks

  2. Phase 2a: Proportion of Participants With Laboratory Abnormalities During the Core Period

    Measured: Up to 16 weeks

  3. Phase 2a: Proportion of Participants With Hb 1.0+ Response

    Hb 1.0+ response is defined as a ≥1.0-g/dL increase from baseline in the average Hb concentration from Week 8 through Week 16

    Measured: Baseline, Week 8 through Week 16

  4. Phase 2a: Change From Baseline in Hb Concentration During the Core Period

    Measured: Baseline up to 16 weeks

  5. Phase 2a: Proportion of Participants With ≥1.5-g/dL increase From Baseline in the Hb Concentration at ≥2 Consecutive Time Points From Week 8 through Week 16

    Measured: Baseline, Week 8 through Week 16

  6. Phase 2a: Change from Baseline in Total Transfused Red Blood Cell (RBC) Units During the Core Period

    Measured: Baseline up to 16 weeks

  7. Phase 2a: Proportion of Participants With ≥50% Reduction in Total Transfused RBC Units for ≥8 Consecutive Weeks During the Core Period Compared With Baseline

    Measured: Baseline up to 16 weeks

  8. Phase 2a: Plasma Concentration of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  9. Phase 2a: Maximum (Peak) Concentration (Cmax) of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  10. Phase 2a: Time to Cmax (tmax) of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  11. Phase 2a: Area Under the Concentration-time Curve From 0 to t Hours (AUC0-t) of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  12. Phase 2a: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval (AUC0-τ) of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  13. Phase 2a: Apparent Terminal Elimination Half-life (t½) of Tebapivat During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  14. Phase 2a: Whole Blood Concentrations of 2,3-diphosphoglycerate (2,3-DPG) During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  15. Phase 2a: Whole Blood Concentrations of Adenosine Triphosphate (ATP) During the Core Period

    Measured: Day 1 and Week 8 (≤60 minutes predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and at Weeks 2, 4, 12, and 16 (≤60 minutes predose)

  16. Phase 2b: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period

    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any AE or suspected adverse reaction that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly/birth defect, or is considered an important medical event.

    Measured: Up to 24 weeks

  17. Phase 2b: Proportion of Participants With Laboratory Abnormalities During the Core Period

    Measured: Up to 24 weeks

  18. Phase 2b: Change From Baseline in Hb Concentration During the Core Period

    Measured: Baseline up to 24 weeks

  19. Phase 2b: Change From Baseline in Total Transfused RBC Units From Week 8 Through Week 24

    Measured: Baseline, Week 8 through Week 24

  20. Phase 2b: Proportion of Participants With ≥50% Reduction in Total Transfused RBC Units for ≥8 Consecutive Weeks During the Core Period Compared With Baseline

    Measured: Baseline up to 24 weeks

  21. Phase 2b: Time to First TI8 During the Core Period

    Measured: Baseline up to 24 weeks

  22. Phase 2b: Proportion of Participants Who Become Transfusion-free for ≥12 Consecutive Weeks (TI12) During the Core Period

    Measured: Up to 24 weeks

  23. Phase 2b: Proportion of Participants With ≥50% Reduction in Total Transfused RBC Units for ≥12 Consecutive Weeks During the Core Period Compared With Baseline

    Measured: Baseline up to 24 weeks

  24. Phase 2b: Time to First TI12 During the Core Period

    Measured: Baseline up to 24 weeks

  25. Phase 2b: Duration of Transfusion Independence (TI)

    The duration of TI will be calculated as the number of days in the longest transfusion-free period starting on or after the start of study treatment through the end of the Core Period.

    Measured: Baseline up to 24 weeks

  26. Phase 2b: Plasma Concentration of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  27. Phase 2b: Maximum (Peak) Concentration (Cmax) of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  28. Phase 2b: Time to Cmax (tmax) of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  29. Phase 2b: Area Under the Concentration-time Curve From 0 to t Hours (AUC0-t) of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  30. Phase 2b: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval (AUC0-τ) of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  31. Phase 2b: Apparent Terminal Elimination Half-life (t½) of Tebapivat During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  32. Phase 2b: Whole Blood Concentrations of 2,3-diphosphoglycerate (2,3-DPG) During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

  33. Phase 2b: Whole Blood Concentrations of Adenosine Triphosphate (ATP) During the Core Period

    Measured: Predose and multiple time points post dose from Day 1 up to Week 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2022
  2. Study start7 Nov 2022
  3. Primary completion17 Mar 2026
  4. Study completionMar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05490446
Sponsor's protocol ID
AG946-C-002
Other IDs
2022-500609-42-00
Status last verified
Sep 2026
First submitted
26 Jul 2022
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tebapivat in people with Myelodysplastic Syndromes, run by Agios Pharmaceuticals, Inc. at 45 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 72 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, Italy, Spain, France, Greece and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 2a: Proportion of Participants With Hemoglobin (Hb) Response (time frame: Baseline, Week 8 through Week 16). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05490446.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.

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