Myelodysplastic syndromes
Conditions
Interventions
Participants will receive the study drug, TAK-226, administered subcutaneously every four weeks (Q4W) for approximately one year during Treatment Period.
Sponsors
Akaike Takenori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participants or their legally authorized representative must be willing and able to sign the ICF and to adhere to the protocol requirements. 2.Japanese adult male or female participant greater than or equal to (>=) 18 years of age at the time of signing informed consent. 3.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 red blood cell (RBC) transfusion and platelet count obtained within 7 days following a platelet transfusion cannot be used to evaluate IPSS-R for eligibility. 4.Transfusion dependent (TD) cohort: Transfusion dependence assessed in the 16 weeks immediately preceding enrollment in two 8-week blocks classified as either: a.Low-transfusion burden (LTB), defined as 4 to 7 RBC units per 16 weeks; or b.High-transfusion burden (HTB), defined as >=8 RBC units per 16 weeks; and c.For all participants: i.Only transfusion events for a pretransfusion Hgb =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. Non-transfusion dependent (NTD) cohort: NTD, defined as 0 to 1 RBC units per 8 weeks immediately preceding enrollment. Note: RBC transfusions administered when Hgb levels were =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treatment, defined as follows: a.Refractory to prior ESA treatment: documentation of nonresponse or a response that was no longer maintained with a prior ESA-containing regimen, either as a single agent or combination (eg, with granulocyte colony-stimulating factor [G-CSF]); ESA regimen must have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
Exclusion criteria
Exclusion criteria: Medical History 1.Del(5q) MDS or therapy-related (secondary) MDS. 2.Anemia due to any other known cause (eg, thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate). 3.Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks in TD cohort or 8 weeks in NTD cohort before enrollment. 4.Clinically significant cardiovascular disease defined as: a.New York Heart Association heart disease class III or IV; b.Fridericia corrected QT (QTcF) interval >500 milliseconds during Screening; c.Presence of uncontrolled hypertension defined as mean systolic blood pressure >=160 mm Hg or diastolic blood pressure >=100 mm Hg during Screening; or d.Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before Screening. 5.Known ejection fraction =5 years. However, participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy: a.Basal or squamous cell carcinoma of the skin; b.Carcinoma in situ of the cervix; c.Carcinoma in situ of the breast; and/or d.Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system). 9.History of solid organ or bone marrow transplantation. 10.Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before enrollment. 11.History of or known active or chronic infection with HIV, active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants who are positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis B surface antibody (HBsAb) may be eligible for enrollment if their hepatitis B viral load is below the limit of detection. Participants who are positive for hepatitis C virus antibodies (HCVAb) may be enrolled if their hepatitis C viral load is below the limit of detection. 12.Body mass index >=40 kg/m^2. 13.Major surgery within 28 days before enrollment. 14.History of allergy/anaphylaxis to investigational medicinal product (IMP) excipients (refer to the current elritercept [TAK 226] IB for a list of excipients) or recombinant proteins. Treatment History 15.TD cohort: Prior use of TAK 226, luspatercept, imetelstat, or sotatercept. NTD cohort: Prior use of TAK 226, luspatercept, imetelstat, sotatercept, or ESAs. Note for NTD cohort: At the investigator's discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of ESAs >=8 weeks prior to enrollment. 16.Prior use of hypomethylating agents (HMAs), isocitrate dehydrogenase inhibitor, lenalidomide, or immunosuppressive therapy given for treatment of MDS. 17.Iron chelation therapy initiated within 8 weeks before enrollment. Participants on stable doses of iron chelation therapy for >=8 weeks are allowed. 18.Vitamin B12 or folate therapy initiated within 4 weeks before enrollment. Participants on stable replacement doses for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.TD cohort: Percentage of Participants Achieving Transfusion Independence (TI) for >= 8 Weeks from Baseline through Week 24 Time Frame: Baseline, Up to Week 24 Transfusion independence is defined as the absence of any red blood cells (RBC) transfusions in a period of at least 8 weeks after the first dose of the study treatment through week 24. 2.NTD cohort: Percentage of Participants Achieving Mean Hgb Increase of >=1.5 g/dL for >=8 Weeks from Baseline through Week 24 And No RBC Transfusion during the Same >=8 Weeks Period Time Frame: Baseline, Up to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.TD cohort: Percentage of Participants Achieving TI for >= 24 Weeks from Baseline through Week 48 Time Frame: Baseline, Up to Week 48 Transfusion independence is defined as the absence of any RBC transfusions in a period of at least 24 weeks after the first dose of the study treatment through week 48. 2.TD cohort: Percentage of Participants with High Transfusion Burden (HTB) Achieving TI >= 8 Weeks from Baseline through Week 24 Time Frame: Baseline, Up to Week 24 Transfusion independence is defined as the absence of any RBC transfusions in a period of at least 8 weeks after the first dose of the study treatment through week 24. 3.TD cohort: Percentage of Participants Achieving Mean Haemoglobin (Hgb) Increase of >= 1.5 g/dL for >= 8 Weeks from Baseline through Week 24 Time Frame: Baseline, Up to Week 24 4.TD cohort: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Time Frame: Up to approximately 6 years An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the trial intervention. A TEAE is defined as an AE that commences on or after the first dose of the study treatment and within 60 days after the last dose of the study treatment, or analysis cutoff date, whichever is earlier. An SAE is any untoward medical occurrence that, at any dose: results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. 5.TD cohort: Change from Baseline in Clinical Laboratory Values, Vital Signs, and Electroc | — |
Contacts
Public ContactContact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
Outcome results
None listed