A study of elritercept to treat transfusion-dependent anemia due to very low, low, or intermediate risk myelodysplastic syndromes

Prior treatment

• Del(5q) MDS or therapy-related (secondary) MDS
• Active infection requiring intravenous treatment (e.g., antibiotics, antifungals, or antivirals) within 28 days, or oral treatment within 14 days before randomization.
• Major surgery within 28 days before randomization
• Prior use of elritercept, luspatercept, sotatercept.
• Prior use of hypomethylating agents (HMA), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive therapy given for treatment of MDS
• Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable 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 concurrent vitamin B12 or folate deficiency are allowed
• Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization.
• Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening

Other illness

• History of or known active or chronic infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
• Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate).
• Estimated glomerular filtration rate < 30 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• Clinically significant cardiovascular disease
• Child-Pugh class C hepatic impairment
• Any known history of AML

Lab values

• Serum EPO level ≥ 500 U/L
• Platelet count ≥ 450 × 109/L or ≤ 25 × 109/L
• Absolute neutrophil count ≤ 500/μL
• Serum aspartate aminotransferase or alanine aminotransferase ≥ 3 × the upper limit of normal
• Total bilirubin ≥ 2 × ULN unless attributable to Gilbert's syndrome
• Ferritin ≤ 50 μg/L
• Known ejection fraction < 35%, confirmed by a local echocardiogram performed during Screening, or other assessment performed echocardiogram if collected within 6 months before Screening

Age

• 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 ≥ 5 years.

Other

• Body mass index ≥ 40 kg/m2
• Folate ≤ 2.0 ng/mL
• Vitamin B12 ≤ 200 pg/mL
• Pregnant or lactating female

• 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 ≥ 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 aspirate collected at Screening, read by an independent central reader) according to WHO 2016 classification that meets the IPSS-R classification of very low, low, or intermediate risk MDS.
• 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: - Only transfusion events for a pretransfusion Hgb < 10 g/dL are counted toward eligibility; - At least 1 transfusion event in each 8-week period and a minimum of 2 transfusion events separated by ≥ 7 days within the 16-week period immediately preceding randomization; and No consecutive 56-day period can be RBC transfusion-free during the 16-week period immediately preceding randomization.
• Refractory or intolerant to prior ESA treatment (discontinued ≥ 4 weeks before randomization), or unlikely to respond to ESA treatment
• Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Females of childbearing potential and sexually active males must agree to use adequate methods