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AG-946 在低危骨髓增生异常综合征 (LR-MDS) 贫血参与者中的研究

2026年9月25日 更新者：Agios Pharmaceuticals, Inc.

一项 2a/2b 期、开放标签、概念验证（2a 期）和双盲、随机、安慰剂对照（2b 期）、多中心、疗效和安全性的 AG-946 研究，用于因低氧血症引起的贫血参与者-风险骨髓增生异常综合征

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.

研究概览

地位

主动，不招人

条件

干预/治疗

研究类型

介入性

注册 (实际的)

87

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 以色列
      • Jerusalem、以色列、9103102
        • Shaare Zedek Medical Center
      • Tel Aviv、以色列
        • Tel Aviv Sourasky Medical Center PPDS
  • 奥地利
    • Upper Austria
      • Linz、Upper Austria、奥地利、4020
        • Ordensklinikum Linz GmbH Elisabethinen
  • 希腊
      • Alexandroupoli、希腊
        • University Hospital of Alexandroupolis
      • Athens、希腊
        • Attikon University General Hospital
      • Pátrai、希腊
        • University General Hospital of Patras
      • Thessaloniki、希腊
        • Hippokration Hospital
  • 德国
    • Lower Saxony
      • Hanover、Lower Saxony、德国、30625
        • Medizinische Hochschule Hannover
    • North Rhine-Westphalia
      • Düsseldorf、North Rhine-Westphalia、德国、40225
        • Universitatsklinikum Dusseldorf
    • Saxony
      • Leipzig、Saxony、德国、04103
        • Universitatsklinikum Leipzig
  • 意大利
      • Roma、意大利
        • Fondazione PTV Policlinico Tor Vergata
    • Lombardy
      • Milan、Lombardy、意大利
        • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
      • Pavia、Lombardy、意大利
        • Fondazione IRCCS Policlinico San Matteo di Pavia
      • Rozzano、Lombardy、意大利
        • Istituto Clinico Humanitas
    • Piedmont
      • Turin、Piedmont、意大利
        • Azienda Ospedaliera Ordine Mauriziano di Torino
  • 捷克语
      • Ostrava、捷克语、708 52
        • Fakultni nemocnice Ostrava
  • 法国
      • Lille、法国、59037
        • CHRU Lille
      • Paris、法国、75475
        • Hôpital Saint Louis
    • Bouches-du-Rhône
      • Marseille、Bouches-du-Rhône、法国、13010
        • Hôpital de La Conception
    • Maine-et-Loire
      • Angers、Maine-et-Loire、法国、49933
        • CHU Angers
  • 波兰
    • Masovian Voivodeship
      • Warsaw、Masovian Voivodeship、波兰
        • MTZ Clinical Research Powered by PRATIA - PPDS
    • Silesian Voivodeship
      • Katowice、Silesian Voivodeship、波兰
        • Pratia Onkologia Katowice - PRATIA - PPDS
    • Warmian-Masurian Voivodeship
      • Olsztyn、Warmian-Masurian Voivodeship、波兰
        • SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
  • 澳大利亚
    • Victoria
      • Clayton、Victoria、澳大利亚、3168
        • Monash Health, Monash Medical Centre
  • 美国
    • California
      • Lakewood、California、美国、90805
        • Innovative Clinical Research Institute Whittier
      • Los Angeles、California、美国、90024
        • David Geffen School of Medicine at UCLA
      • Redlands、California、美国、92373
        • Emad Ibrahim, MD, Inc.
    • Connecticut
      • New Haven、Connecticut、美国、06510
        • Smilow Cancer Hospital at Yale New Haven
    • Florida
      • Jacksonville、Florida、美国、32224
        • Mayo Clinic Jacksonville - PPDS
    • Illinois
      • Skokie、Illinois、美国、60076
        • Edward H. Kaplan MD & Associates
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University School of Medicine
    • New York
      • Long Island City、New York、美国、11101
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Durham、North Carolina、美国、27705
        • Duke Adult Blood and Marrow Clinic
  • 英国
      • Edinburgh、英国、EH24 2XU
        • Western General Hospital Edinburgh - PPDS
      • London、英国、SE5 9RS
        • Kings College Hospital
      • Oxford、英国、OX3 7LE
        • Churchill Hospital-NHS Oxford
    • Aberdeen City
      • Aberdeen、Aberdeen City、英国、AB25 2ZN
        • Aberdeen Royal Infirmary - PPDS
  • 西班牙
      • Córdoba、西班牙、14004
        • C.H. Regional Reina Sofia - PPDS
      • Madrid、西班牙、28046
        • Hospital Universitario La Paz - PPDS
      • Madrid、西班牙、28050
        • Hospital Universitario HM Sanchinarro - CIOCC
      • Salamanca、西班牙、37007
        • Complejo Asistencial Universitario de Salamanca - H. Clinico
      • Seville、西班牙、41013
        • Hospital Universitario Virgen del Rocio - PPDS
  • 韩国
      • Daegu、韩国、41944
        • Kyungpook National University Hospital
      • Seoul、韩国、05505
        • Asan Medical Center - PPDS
      • Seoul、韩国
        • The Catholic University of Korea, Seoul St. Mary's Hospital

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

Phase 2a

  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.

Phase 2b

  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

    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.

  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.

Exclusion Criteria:

Phase 2a

  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).

Phase 2b

  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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Core Period: Phase 2a - Tebapivat 5 mg

Participants 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.
药品：Tebapivat

Tebapivat Tablet

其他名称：
  • AG-946
实验性的：Core Period: Phase 2b - Tebapivat 10 mg

Participants 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.
药品：Tebapivat

Tebapivat Tablet

其他名称：
  • AG-946
实验性的：Core Period: Phase 2b - Tebapivat 15 mg

Participants 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.
药品：Tebapivat

Tebapivat Tablet

其他名称：
  • AG-946
实验性的：Core Period: Phase 2b - Tebapivat 20 mg

Participants 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.
药品：Tebapivat

Tebapivat Tablet

其他名称：
  • AG-946

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Phase 2a: Proportion of Participants With Hemoglobin (Hb) Response
大体时间：Baseline, Week 8 through Week 16

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.
Baseline, Week 8 through Week 16
Phase 2a: Proportion of Participants With Transfusion Independence During the Core Period
大体时间：Up to 16 weeks

Transfusion Independence is defined as transfusion-free for ≥8 consecutive weeks during the Core Period (participants With Low Transfusion Burden [LTB] only).
Up to 16 weeks
Phase 2b: Proportion of Participants With Transfusion Independence
大体时间：Up to 24 weeks

Transfusion independence, defined as transfusion-free for ≥8 consecutive weeks (TI8) during the Core Period.
Up to 24 weeks

次要结果测量

结果测量
措施说明
大体时间
阶段 2a：核心期 Hb 浓度相对于基线的变化
大体时间：长达 16 周的基线
长达 16 周的基线
2a 期：核心时期输注红细胞 (RBC) 总量相对于基线的变化
大体时间：长达 16 周的基线
长达 16 周的基线
阶段 2a：核心期 2,3-二磷酸甘油酸 (2,3-DPG) 的全血浓度
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期三磷酸腺苷 (ATP) 的全血浓度
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 2b 阶段：从第 8 周到第 24 周输注红细胞总数相对于基线的变化
大体时间：基线，第 8 周至第 24 周
基线，第 8 周至第 24 周
第 2a 阶段：核心期内出现实验室异常的参与者比例
大体时间：长达 16 周
长达 16 周
第 2a 阶段：从第 8 周到第 16 周，在 ≥2 个连续时间点，血红蛋白浓度较基线增加 ≥1.5 g/dL 的参与者比例
大体时间：基线，第 8 周至第 16 周
基线，第 8 周至第 16 周
第 2a 阶段：与基线相比，在核心期内连续 8 周内总输血红细胞单位减少 ≥50% 的参与者比例
大体时间：基线长达 16 周
基线长达 16 周
阶段 2a：核心期间 Tebapivat 的血浆浓度
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期间 Tebapivat 的最大（峰值）浓度 (Cmax)
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期内 Tebapivat 达到 Cmax (tmax) 的时间
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期间 Tebapivat 从 0 到 t 小时 (AUC0-t) 的浓度-时间曲线下面积
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期内从 0 到 Tebapivat 给药间隔结束 (AUC0-τ) 的浓度-时间曲线下面积
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
阶段 2a：核心期内 Tebapivat 的表观终末消除半衰期 (t½)
大体时间：第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 1 天和第 8 周（给药前≤60 分钟和给药后 0.5、1、2、3、4、6 和 8 小时）以及第 2、4、12 和 16 周（给药前≤60 分钟）
第 2b 阶段：核心期内出现实验室异常的参与者比例
大体时间：长达 24 周
长达 24 周
第 2b 阶段：核心期内 Hb 浓度相对于基线的变化
大体时间：基线长达 24 周
基线长达 24 周
第 2b 阶段：与基线相比，在核心期内连续 8 周内总输血红细胞单位减少 ≥50% 的参与者比例
大体时间：基线长达 24 周
基线长达 24 周
第 2b 阶段：核心期间首次 TI8 的时间
大体时间：基线长达 24 周
基线长达 24 周
第 2b 阶段：核心期内连续 ≥12 周 (TI12) 不再输血的参与者比例
大体时间：长达 24 周
长达 24 周
第 2b 阶段：与基线相比，在核心期内连续 12 周内总输血红细胞单位减少 ≥50% 的参与者比例
大体时间：基线长达 24 周
基线长达 24 周
第 2b 阶段：核心期间首次 TI12 的时间
大体时间：基线长达 24 周
基线长达 24 周
阶段 2b：核心期间 Tebapivat 的血浆浓度
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
阶段 2b：核心期间 Tebapivat 的最大（峰值）浓度 (Cmax)
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
阶段 2b：核心期内 Tebapivat 达到 Cmax (tmax) 的时间
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
阶段2b：核心期间Tebapivat从0到t小时（AUC0-t）的浓度-时间曲线下面积
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
阶段 2b：核心期间从 0 到 Tebapivat 给药间隔结束 (AUC0-τ) 的浓度-时间曲线下面积
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
阶段 2b：核心期内 Tebapivat 的表观终末消除半衰期 (t½)
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
第 2b 阶段：核心期间 2,3-二磷酸甘油酯 (2,3-DPG) 的全血浓度
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
第 2b 阶段：核心期三磷酸腺苷 (ATP) 的全血浓度
大体时间：给药前和给药后多个时间点（从第 1 天到第 20 周）
给药前和给药后多个时间点（从第 1 天到第 20 周）
Phase 2a: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period
大体时间：Up to 16 weeks

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.
Up to 16 weeks
Phase 2a: Proportion of Participants With Hb 1.0+ Response
大体时间：Baseline, Week 8 through Week 16

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
Baseline, Week 8 through Week 16
Phase 2b: Proportion of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation During the Core Period
大体时间：Up to 24 weeks

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.
Up to 24 weeks
Phase 2b: Duration of Transfusion Independence (TI)
大体时间：Baseline up to 24 weeks

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.
Baseline up to 24 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Agios Pharmaceuticals, Inc.

调查人员

  • 学习椅：Medical Medical Affairs、Agios Pharmaceuticals, Inc.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年11月7日

初级完成 (实际的)

2026年3月17日

研究完成 (估计的)

2029年3月1日

研究注册日期

首次提交

2022年7月26日

首先提交符合 QC 标准的

2022年8月4日

首次发布 (实际的)

2022年8月5日

研究记录更新

最后更新发布 (实际的)

2026年9月28日

上次提交的符合 QC 标准的更新

2026年9月25日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • AG946-C-002
  • 2022-500609-42-00 (其他标识符：EU-CTR)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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