A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions

The main aim of this study is to find out how well elritercept works in lowering the need for RBC transfusions. Other aims are to learn how well elritercept works in reducing the need for RBC transfusions over longer periods of time or in adults with high transfusion needs. The study will also check on how safe elritercept is and how well it is tolerated.

Inclusion Criteria: * Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information and/or protected personal data in accordance with national and local study participant data protections and privacy regulations. * Male or female greater than or equal to (≥)18 years of age at the time of signing informed consent. * Diagnosis of MDS with or without RS (as determined in an evaluable bone marrow sample, read by an independent central reader to confirm diagnosis at Screening) according to the World Health Organization 2016 classification that meets the International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease. In cases where a local bone marrow (BM) assessment establishing an MDS diagnosis was conducted within 12 weeks prior to informed consent form (ICF) signature, the associated local BM samples and/or reports may be permitted. * Transfusion dependence assessed in the 16 weeks immediately preceding randomization in two 8-week blocks, classified as either: a. LTB, defined as 4 to 7 RBC units per 16 weeks; or b. HTB, defined as ≥8 RBC units per 16 weeks; and c. For all participants: i. Only transfusion events for a pretransfusion hemoglobin (Hgb) lesser than (\)200 units per liter (U/L). * Less than 5 percent (%) blasts in an evaluable bone marrow sample collected at Screening. * Eastern Cooperative Oncology Group performance status of 0 to 2. * Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception. * In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits). Exclusion Criteria: * Del(5q) MDS, secondary MDS (MDS with a documented history of prior exposure to chemotherapy, radiotherapy, or other leukemogenic agents that is considered causally related to the development of MDS). * Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate). * Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization. * Clinically significant cardiovascular disease defined as: 1. New York Heart Association heart disease class III or IV; 2. Fridericia corrected QT (QTcF) interval \>500 milliseconds during Screening; 3. Presence of uncontrolled hypertension defined as mean systolic blood pressure ≥160 millimeters of mercury (mm Hg) or diastolic blood pressure ≥100 mm Hg during Screening; or 4. Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before Screening. * Known ejection fraction \ 200 cells per microliter (cells/μL) at screening. Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines. * Body mass index ≥ 40 kilograms per meter square (kg/m\^2). * Major surgery within 28 days before randomization. * History of allergy/anaphylaxis to investigational medicinal product (IMP) excipients (refer to the current elritercept IB for a list of excipients) or recombinant proteins. * Prior use of elritercept, luspatercept, or sotatercept. * Prior use of hypomethylating agents (HMAs), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immunosuppressive therapy given for treatment of MDS. * Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable or decreasing doses of iron chelation therapy for ≥ 8 weeks are allowed. * Vitamin B12 or folate therapy initiated within 4 weeks before randomization. Participants on stable replacement doses for ≥ 4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed. * Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for ≥ 8 weeks are allowed. * High-dose systemic corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone lesser than or equal to (≤) 10 milligrams per day (mg/day) or corticosteroid equivalent for ≥ 4 weeks are allowed.10 mg/day or corticosteroid equivalent for ≥ 4 weeks are allowed. * Treatment with any investigational drug within 28 days before Screening or, if the half-life of the product is known, within 5 times the half-life before Screening, whichever is longer. * Ongoing participation in another interventional clinical study. * Serum EPO level \>500 U/L. * Platelet count ≥800 × 10\^9 per liter (/L) or ≤25 × 10\^9/L. * Absolute neutrophil count ≤ 500 per microliter (/µL). * Serum aspartate aminotransferase or alanine aminotransferase ≥3 × the upper limit of normal (ULN). * Total bilirubin ≥2 × ULN unless attributable to Gilbert's syndrome. Participants with known history of Gilbert syndrome with unconjugated bilirubin \< 3 × ULN are allowed. Higher levels, if attributed to active RBC precursor destruction within the bone marrow (ineffective erythropoiesis), may be allowed upon medical monitor review. * Ferritin ≤ 50 micrograms per litre (μg/L). * Folate ≤2.0 nanograms per milliliter (ng/mL). * Vitamin B12 ≤200 picograms per milliliter (pg/mL). * Estimated glomerular filtration rate \