Myelodysplastic syndromes
Conditions
Interventions
Elritercept
Participants will receive a starting dose of elritercept at 3.75 milligrams per kilogram (mg/kg) administered subcutaneously (SC) once every 4 weeks, and may have the dose escalated to 5.0
Sponsors
Akaike Takenori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female participants aged >= 18 years or older at time of signing the informed consent form (ICF). 2.Able to understand the purpose and risks of the trial and voluntarily sign an ICF prior to any trial-related procedures being conducted and authorization to use protected health information and personal data in accordance to national and local privacy regulations. 3.Documented diagnosis of myelodysplastic syndrome(s) (MDS) according to WHO 2016 classification that meets International Prognostic Scoring System -Revised (IPSS-R) classification of very low-, low-, or intermediate-risk disease, confirmed by central laboratory independent reviewer prior to randomization. Hemoglobin (Hgb), platelet, and absolute neutrophil count (ANC) values should be collected greater than (>) 14 days after red blood cell (RBC) transfusion or greater than (>) 7 days after platelet transfusion, unless otherwise considered to be pretransfusion values. 4.Bone marrow less than (14 days following an RBC transfusion to evaluate for eligibility unless considered pretransfusion values. 6.Participant requires RBC transfusion, as documented by the following criteria. A transfusion requirement of 2 to 6 pRBCs units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization. -Hgb levels at the time of or within 3 days prior to administration of a RBC transfusion must have been less than or equal to (9.0 g/dL (or >7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification. 7.Hgb <11.0 g/dL (6.8 mmol/L) after last RBC transfusion preceding randomization. Local laboratory is acceptable to facilitate randomization. 8.Eastern Cooperative Oncology Group score of 0, 1, or 2.
Exclusion criteria
Exclusion criteria: 1.Prior therapy with any of the following: a.Epoetin alfa -At the investigator's discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of only epoetin alfa >=8 weeks prior to randomization. No other erythropoiesis-stimulating agent (ESA) agent is allowed. b.Darbepoetin. c.Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administered =8 weeks prior to randomization. e.Hypomethylating agent. -At the investigator's discretion, in consultation with the medical monitor may be allowed if received no more than 2 doses >=8 weeks prior to randomization. f.Luspatercept, sotatercept, imetelstat, or elritercept. g.Immunosuppressive therapy. h.Hematopoeitic cell transplant. i.Iron chelation if administered =8 weeks are allowed Vitamin B12 or folate therapy initiated within 4 weeks prior to randomization. Participants on stable replacement doses for >=4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed. j.Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for >=8 weeks are allowed. k.High-dose corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone = 4 weeks are allowed. Other disease modifying treatments for autoimmune diseases may be allowed upon medical monitor review. l.Investigational agent or any other agent intended for treatment MDS treatment. 2.Diagnosed to have MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable according to WHO 2016 classification or secondary MDS. 3.Known history of diagnosis of acute myeloid leukemia (AML). 4.Anemia due to any other known cause including but not limited to thalassemia; hypothyroidism; due to iron, vitamin B12, vitamin B6, zinc, or folate deficiencies; autoimmune or hereditary hemolytic anemia; any type of known clinically significant bleeding or sequestration or drug induced anemia, hemolytic anemia, or bleeding events. 5.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.Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening. 6.Known ejection fraction =160 millimeters
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Proportion of Participants who Are RBC Transfusion Independent (RBC -TI) for any Consecutive Greater Than Equal to (>=) 12-Week Period from Day 1 Through 24 Weeks With Concurrent Mean Hemoglobin (Hgb) Increase >=1.5 Grams per Deciliter (g/dL) from Baseline Time Frame: From Cycle 1 Day 1 (C1D1) through Week 24 RBC-TI is defined as no red blood cell (RBC) transfusions administered for the specified time period during study treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Proportion of Participants who Are RBC-TI for any Consecutive >=16-Week Period from Day 1 to 24 Weeks Time Frame: From C1D1 through Week 24 2.Proportion of Participants who Are RBC-TI for any Consecutive >=12-Week Period from Day 1 to 24 Weeks Time Frame: From C1D1 through Week 24 3.Proportion of Participants who Are RBC-TI for a Consecutive 24-Week Period from Day 1 Time Frame: From C1D1 through Week 24 4.Proportion of Participants who Have Confirmed Meaningful Improvement or no Meaningful Deterioration in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score With no RBC Transfusions Between Week 12 to Week 24 Time Frame: From End of Week 12 to End of Week 24 The FACT-An questionnaire is used to assess the effects of disease symptoms on functioning and well-being in participants with anemia. The FACT-An Anemia scale includes 13 fatigue-specific items (which together comprise the FACIT-Fatigue scale). 5.Proportion of Participants who Achieved Hematological Improvement-Erythroid (HI-E) for a Minimum 8-Week Period and for a Minimum 12-Week Period from Day 1 to 24 Weeks And up to 48 Weeks Time Frame: From Week 1 to Week 24 and 48 HI-E is defined as percentage of participants meeting HI-E criteria sustained over any consecutive 56-day period over the first 24 weeks. 6.Proportion of Participants who are RBC-TI for a Minimum Consecutive 8-Week Period from Day 1 to 24 Weeks Time Frame: From C1D1 through Week 24 7.Proportion of Participants who Are RBC-TI for a Minimum Consecutive 24-Week Period from Day 1 to 48 Weeks Time Frame: From C1D1 through Week 48 8.Time from Date of First Dose to First Onset of Achieving RBC-TI Time Frame: From C1D1 through Week 24 RBC-TI is defined as the absence of RBC transfusions for a prespecified period of time during continued treatment. Time from date of first dose to first onset of achieving RBC-TI for minimum consecutive 12 weeks and for minimum consecutive 16 weeks. 9.Mean Hgb Change from Baseline Throug | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, Hungary, India, Ireland, Italy, Japan, Lithuania, Malayasia, Mexico, Norway, Poland, Romania, Spain, Taiwan, Thailand, the Netherlands, Turkey, United Kingdom, United States
Contacts
Public ContactContact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
Outcome results
None listed