A Phase 2, Multicenter, Open-Label, Single-arm Study to Evaluate the Efficacy and Safety of TAK-226 for Anemia in Japanese Patients With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes
The main aim of the study is to evaluate how TAK-226 improves symptoms of transfusion-dependent anemia in Japanese patients with lower-risk myelodysplastic syndromes. The study consists of Screening Period (up to 6 weeks), Treatment Period, Safety Follow-Up Period (8 weeks), and Long-Term Follow-Up Period (5 years from the first dose of the study drug or 3 years after the last dose, whichever is longer). Participants of this study will be administered TAK-226 during Treatment Period. Subsequently, the participants will be monitored for side effects related to the study treatment during Safety Follow-Up Period and Long-Term Follow-Up Period. The approximate duration of participation for a participant is up to approximately 6 years. During the study period, participants will visit the study clinic/hospital multiple times as per the study schedule. During Treatment Period, the participants will come to the clinic/hospital approximately every two to four weeks.
• Participants or their legally authorized representative must be willing and able to sign the ICF and to adhere to the protocol requirements.
• Japanese adult male or female participant \>=18 years of age at the time of signing informed consent.
• Diagnosis of MDS with or without ring sideroblasts (RS) (as determined in an evaluable bone marrow aspirate collected at Screening to confirm diagnosis) according to WHO 2016 classification that meets the International Prognostic Scoring System-Revised (IPSS-R) classification of very low-, low-, or intermediate-risk MDS.
• Note: Due to expected impacts of transfusion, hemoglobin (Hgb) values from blood samples collected within 14 days following a RBC transfusion and platelet count obtained within 7 days following a platelet transfusion cannot be used to evaluate IPSS-R for eligibility.
• TD\[YY1.1\] cohort: Transfusion dependence assessed in the 16 weeks immediately preceding enrollment in two 8-week blocks classified as either:
‣ Low-transfusion burden (LTB), defined as 4 to 7 RBC units per 16 weeks; or
⁃ HTB\[YY2.1\], defined as \>=8 RBC units per 16 weeks; and
⁃ For all participants: i. Only transfusion events for a pretransfusion Hgb \<10 g/dL are counted toward eligibility; ii. At least 1 transfusion event in each 8-week block and a minimum of 2 transfusion events separated by \>=7 days within the 16-week period immediately preceding enrollment; and iii. No consecutive 56-day period can be RBC transfusion-free during the 16 week period immediately preceding enrollment.
• Note: Only transfusions for the disease under study will be counted towards classification for LTB or HTB participants. Transfusions for intercurrent diseases (bleeding, surgical procedure, infection, etc.) are not considered.
• NTD\[YY3.1\] cohort: NTD, defined as 0 to 1 RBC units per 8 weeks immediately preceding enrollment.
• Note: RBC transfusions administered when Hgb levels were \<9.0 g/dL are counted for eligibility. RBC transfusions administered for other than MDS-related anemia (bleeding, surgical procedure, infection, etc.) will not be counted as a required transfusion for the purpose of meeting eligibility criteria.
• TD cohort: Refractory or intolerant to prior erythropoiesis-stimulating agent (ESA) treatment (discontinued \>=4 weeks before enrollment), or unlikely to respond to ESA treatment, defined as follows:
• a. Refractory to prior ESA treatment: documentation of nonresponse or a response that was no longer maintained with a prior ESA-containing regimen, either as a single agent or combination (eg, with granulocyte colony-stimulating factor \[G-CSF\]); ESA regimen must have been either: i. Recombinant human erythropoietin (EPO) \>=40,000 IU/week for \>=8 doses or equivalent; or ii. Darbepoetin alpha \>=500 mcrg every 3 weeks for \>=4 doses or equivalent. b. Intolerant to prior ESA treatment: documentation of discontinuation of a prior ESA containing regimen, either as a single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an AE.
• c. Unlikely to respond to ESA treatment: low chance of response to ESA based on an endogenous serum EPO level \>200 U/L.
• Note: Due to expected impacts of transfusion on EPO levels, blood samples collected within the 14 days following an RBC transfusion or within 7 days following a platelet transfusion cannot be used to evaluate serum EPO level for eligibility.
• NTD cohort: Hgb \<10 g/dL and exhibiting anemia-related clinical symptoms (eg, fatigue, shortness of breath, or others) during screening.
• Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Women of childbearing potential (WOCBP), defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months must
‣ Agree to use 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 60 days after the last dose of study drug; or
⁃ Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
• Male participants must, even if he is surgically sterilized (ie, status postvasectomy),
‣ Agree to practice effective barrier contraception the time of signing the informed consent through 60 days after the last dose of study drug; or
⁃ Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)