ACTIVE_NOT_RECRUITING

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

Conditions

Myelodysplastic Syndromes Anemia Lower-Risk Myelodysplastic Syndromes

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2022-11-07

Study Completion:2029-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05490446

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. At least 18 years of age at the time of providing informed consent; 2. 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; 3. 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; 4. A hemoglobin (Hb) concentration \<11.0 grams per deciliter (g/dL) during the 4-week Screening Period; 5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2; 6. 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; 7. 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; 8. 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. 1. At least 18 years of age at the time of providing informed consent; 2. 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; 3. With LTB, or high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria: 1. 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 2. 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 4. 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 5. A Hb concentration \<10.0 g/dL during the 4-week Screening Period; 6. Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin \[EPO\], EPO + granulocyte colony-stimulating factor \[G-CSF\]) and/or luspatercept; 7. ECOG Performance Status score of 0, 1, or 2; 8. 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; 9. 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; 10. 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.	1. Known history of acute myeloid leukemia (AML); 2. 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; 3. 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; 4. 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; 5. 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; 6. 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; 7. Renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) \<45 milliliters per minute (mL/min)/1.73 m\^2; 8. 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; 9. 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; 10. 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; 11. Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg); 12. Positive test for HIV-1 Ab or HIV-2 Ab; 13. Absolute neutrophil count (ANC) \<500/microliter (μL) (0.5 × 10\^9/L); 14. Platelet count ≤75,000/μL during Screening (75 × 10\^9/L) platelet transfusions within 28 days before Screening or during Screening; 15. Nonfasting triglyceride concentration \>500 mg/dL; 16. 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; 17. 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; 18. Known allergy to tebapivat or its excipients; 19. Pregnant or breastfeeding; 20. 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). 1. Known history of AML; 2. 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; 3. 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; 4. 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; 5. 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 6. 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 7. Renal dysfunction, as defined by an eGFR \<45 mL/min/1.73 m\^2; 8. 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; 9. 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; 10. 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.; 11. Positive test for HCV Ab with evidence of active HCV infection, or positive test for HBsAg; 12. Positive test for HIV-1 Ab or HIV-2 Ab; 13. ANC \<500/μL (0.5 × 10\^9/L); 14. Platelet count \< 75,000/μL (75 × 10\^9 /L) during Screening; platelet transfusions within 28 days before Screening or during Screening; 15. Nonfasting triglyceride concentration \>500 mg/dL; 16. 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; 17. 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; 18. Known allergy to tebapivat or its excipients; 19. Pregnant or breastfeeding; 20. 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). 21. 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.

Inclusion Criteria

Exclusion Criteria

1. At least 18 years of age at the time of providing informed consent;
2. 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;
3. 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;
4. A hemoglobin (Hb) concentration \<11.0 grams per deciliter (g/dL) during the 4-week Screening Period;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2;
6. 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;
7. 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;
8. 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.
1. At least 18 years of age at the time of providing informed consent;
2. 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;
3. With LTB, or high transfusion burden (HTB), based on transfusion history from the participant's medical record, according to revised IWG 2018 criteria:
1. 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
2. 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
4. 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
5. A Hb concentration \<10.0 g/dL during the 4-week Screening Period;
6. Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin \[EPO\], EPO + granulocyte colony-stimulating factor \[G-CSF\]) and/or luspatercept;
7. ECOG Performance Status score of 0, 1, or 2;
8. 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;
9. 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;
10. 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.

1. Known history of acute myeloid leukemia (AML);
2. 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;
3. 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;
4. 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;
5. 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;
6. 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;
7. Renal dysfunction, as defined by an estimated glomerular filtration rate (eGFR) \<45 milliliters per minute (mL/min)/1.73 m\^2;
8. 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;
9. 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;
10. 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;
11. Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);
12. Positive test for HIV-1 Ab or HIV-2 Ab;
13. Absolute neutrophil count (ANC) \<500/microliter (μL) (0.5 × 10\^9/L);
14. Platelet count ≤75,000/μL during Screening (75 × 10\^9/L) platelet transfusions within 28 days before Screening or during Screening;
15. Nonfasting triglyceride concentration \>500 mg/dL;
16. 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;
17. 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;
18. Known allergy to tebapivat or its excipients;
19. Pregnant or breastfeeding;
20. 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).
1. Known history of AML;
2. 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;
3. 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;
4. 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;
5. 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
6. 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
7. Renal dysfunction, as defined by an eGFR \<45 mL/min/1.73 m\^2;
8. 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;
9. 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;
10. 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.;
11. Positive test for HCV Ab with evidence of active HCV infection, or positive test for HBsAg;
12. Positive test for HIV-1 Ab or HIV-2 Ab;
13. ANC \<500/μL (0.5 × 10\^9/L);
14. Platelet count \< 75,000/μL (75 × 10\^9 /L) during Screening; platelet transfusions within 28 days before Screening or during Screening;
15. Nonfasting triglyceride concentration \>500 mg/dL;
16. 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;
17. 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;
18. Known allergy to tebapivat or its excipients;
19. Pregnant or breastfeeding;
20. 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).
21. 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.

Contacts and Locations

Principal Investigator

Medical Medical Affairs

STUDY_CHAIR

Agios Pharmaceuticals, Inc.

Study Locations (Sites)

Innovative Clinical Research Institute Whittier

Lakewood, California, 90805

United States

David Geffen School of Medicine at UCLA

Los Angeles, California, 90024

United States

Emad Ibrahim, MD, Inc.

Redlands, California, 92373

United States

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510

United States

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224

United States

Edward H. Kaplan MD & Associates

Skokie, Illinois, 60076

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Memorial Sloan Kettering Cancer Center

Long Island City, New York, 11101

United States

Duke Adult Blood and Marrow Clinic

Durham, North Carolina, 27705

United States

Collaborators and Investigators

Sponsor: Agios Pharmaceuticals, Inc.

Medical Medical Affairs, STUDY_CHAIR, Agios Pharmaceuticals, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-07

Study Completion Date2029-03

Study Record Updates

Study Start Date2022-11-07

Study Completion Date2029-03

Terms related to this study

Keywords Provided by Researchers

Anemia
Lower-Risk Myelodysplastic Syndromes

Additional Relevant MeSH Terms

Myelodysplastic Syndromes