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

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 \<35%, confirmed by a local echocardiogram performed during Screening, or a previously performed echocardiogram if collected within 6 months before Screening. • Child-Pugh class C hepatic impairment. • Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening. • Any known history of acute myeloid leukemia (AML). • Prior history of malignancies, other than MDS, unless participant has been free of the disease (including completion of any treatment, including maintenance, for prior malignancy) for ≥ 2 years. However, participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy: 1. Basal or squamous cell carcinoma of the skin; 2. Carcinoma in situ of the cervix; 3. Carcinoma in situ of the breast; and/or 4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis \[TNM\] clinical staging system). 5. Early papillary thyroid cancer (stage I \[T1-T2, N0, M0\]). • History of solid organ or bone marrow transplantation. • Active infection requiring intravenous treatment (e.g., antibiotics, antifungals, or antivirals) within 28 days, or oral treatment within 14 days before randomization. • Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Participants with a history of HIV infection may be enrolled if they are receiving antiretroviral therapy and have a documented CD4+ T cell count \> 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 \<30 milliliters per minute per 1.73 meter square (mL/min/1.73m\^2) as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration equation. • Pregnant or lactating female. • Any other condition not specifically noted above that, in the opinion of the Investigator, would preclude the participant from participating in the study or could confound interpretation of data from the study. • Investigational site staff members directly involved in the conduct of the study and site staff members otherwise supervised by the Investigator, employees of the Sponsor or CRO directly involved in the conduct of the study, or immediate family members (defined as a spouse, parent, child, or sibling, whether biological or legally adopted). • For Participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults (per applicable French law \[Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1\]).