A phase IIa/IIb, open-label, proof of concept (Phase IIa) and double-blind, randomized, placebo-controlled (phase IIb), multicenter, efficacy, and safety study of AG-946 in participants with anemia due to lower-risk myelodysplastic syndromes

Agios Pharmaceuticals (United States)0 个研究点目标入组 116 人开始时间: 2022年10月11日最近更新: 2023年1月30日

适应症

试验速览

阶段: 2 期
状态: 进行中（未招募）
发起方
入组人数: 116

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

性别: All

入选标准

•1. At least 18 years of age at the time of providing informed consent
•2. Documented diagnosis of MDS according to World Health Organization (WHO) classification, 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. Nontransfused or with LTB, based on transfusion history from the participant’s medical record, according to revised IWG 2018 criteria:
•a. NTD: <3 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
•b. LTB: 3 to 7 RBC units in the 16-week period before administration of the first dose of the study drug and <4 RBC units in the 8-week period before administration of the first dose of the study drug
•4. An Hb concentration <11.0 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 the study drug
•7. For women of childbearing potential (WOCBP) and men with partners who are WOCBP, must be abstinent from sexual activities that may result in a pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug for women and 90 days after the last dose of study drug for men. The second form of contraception can be an acceptable barrier method
•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 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. Nontransfused, with LTB, or with HTB, based on transfusion history from the participant’s medical record, according to revised IWG 2018 criteria:
•a. NTD: <3 RBC units in the 16-week period before randomization and no transfusions in the 8-week period before randomization, or
•b. LTB: 3 to 7 RBC units in the 16-week period before randomization and <4 RBC units in the 8-week period before randomization, or
•c. HTB: =8 RBC units in the 16-week period before randomization and =4 RBC units in the 8-week period before randomization
•4. An Hb concentration <11.0 g/dL during the 4-week Screening Period
•5. Up to 2 prior therapies including erythropoiesis-stimulating agents (ESAs) (eg, erythropoietin [EPO], EPO + granulocyte colony-stimulating factor [G-CSF]) and/or luspatercept
•6. ECOG Performance Status score of 0, 1, or 2
•7. If taking iron chelation therapy, the iron chelation therapy dose must hav

排除标准

•Phase IIa and Phase IIb:
•1. Known history of acute myeloid leukaemia (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, treatment administered for high-risk MDS (hypomethylating agents [HMAs], isocitrate dehydrogenase [IDH] inhibitors, or allogeneic or autologous stem cell transplant), and/or disease-modifying agents (eg, immunomodulatory drugs such as lenalidomide). If a participant received =1 week of treatment with a disease-modifying agent =8 weeks before administration of the first dose of the study drug, then they may not be excluded, at the Investigator’s discretion.
•4. Currently receiving treatment with luspatercept, EPO, or G-CSF. Treatment with EPO or G-CSF must have been stopped for =28 days before administration of the first dose of the study drug; treatment with luspatercept must have been stopped for =65 days before administration of the first dose of the 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: a. New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia; b. Myocardial infarction, unstable angina pectoris, or unstable hypertension; high-risk thrombosis; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism; c. 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; d. Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis >50%; e. 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: a. Serum AST >2.5 × upper limit of normal (ULN) (unless due to haemolysis and/or hepatic iron deposition) and ALT >2.5 × ULN (unless due to hepatic iron deposition); b. 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 mL/min
•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 the study drug.
•9. Major surgery within 12 weeks before administration of the first dose of the study drug. Participants must have completely recovered from any previous surgery before administration of the first dose of the study drug.
•10. History of any malignancy, except for non-melanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ. Participants must not have active disease or have received anticancer treatment =5 years before provi

研究者

发起方

Agios Pharmaceuticals (United States)

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