Phase 3 Randomized Double-Blind Placebo-Controlled Trial of Elritercept in Transfusion-Dependent Anemia in Myelodysplastic Syndromes

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of elritercept in reducing red blood cell (RBC) transfusions in adult participants with transfusion-dependent anemia due to very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS). This is clinically relevant as reducing the need for RBC transfusions can significantly improve the quality of life and reduce the complications associated with frequent transfusions in patients with MDS.

Secondary objectives include:

• To evaluate the efficacy of elritercept in reducing RBC transfusions over longer intervals and/or in participants with high-transfusion burden (HTB).
• To assess the safety and tolerability of elritercept.

The clinical trial involves a total of **153 participants** diagnosed with **myelodysplastic neoplasms/syndromes (MDS)**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific criteria, including a diagnosis of MDS according to the WHO 2016 classification, with a risk classification of very low, low, or intermediate as per the IPSS-R. The trial population is transfusion-dependent, having received a defined number of red blood cell transfusions in the 16 weeks preceding randomization. Participants must have an Eastern Cooperative Oncology Group performance status of 0 to 2 and be refractory or intolerant to prior ESA treatment. The study includes individuals who are part of a vulnerable population, and both genders are represented. Lifestyle considerations such as diet and physical activity are not specified. The trial does not provide additional information on the general health status or specific lifestyle habits of the participants.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **elritercept** (KER-050) in treating transfusion-dependent anemia in adult participants with very low, low, or intermediate-risk **myelodysplastic syndromes** (MDS). The trial aims to assess the reduction in red blood cell (RBC) transfusions among participants. The study is expected to commence recruitment on April 17, 2025, and conclude by April 1, 2032. Participants will be randomly assigned to receive either elritercept or a placebo, both administered as a solution for injection via subcutaneous use.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis of MDS, transfusion dependence, and prior treatment history. Participants must be 18 years or older, have a confirmed diagnosis of MDS with specific risk classifications, and demonstrate transfusion dependence. The screening will involve a bone marrow aspirate evaluated by an independent central reader. Following randomization, participants will undergo regular follow-up visits to monitor efficacy and safety outcomes, including the primary endpoint of achieving transfusion independence for at least 8 weeks from baseline through week 24. Secondary endpoints include achieving transfusion independence for 24 weeks, incidence of treatment-emergent adverse events, and changes in clinical laboratory values.

The expected duration of participant involvement is up to 48 weeks, with the possibility of early termination if specific conditions arise, such as adverse events or withdrawal of consent. Participants will be closely monitored throughout the study, with the end-of-study visit marking the completion of their involvement. This visit will include a final assessment of safety and efficacy outcomes. The trial is structured to ensure rigorous evaluation of elritercept's potential benefits and risks in the target population, adhering to high standards of clinical research methodology.

The clinical trial involves the administration of **elritercept**, a solution for injection, as the experimental medication. Elritercept is a protein-based therapeutic agent, specifically an activin receptor type-2A extracellular domain modified and fused to the human IgG1 Fc domain. It is administered subcutaneously. The dosing regimen for elritercept is based on body weight, with a maximum daily dose of 5.0 mg/kg and a total maximum dose of 65 mg over the course of the treatment. The treatment period extends up to 12 weeks. The pharmaceutical form of elritercept is a solution for injection, and it is manufactured by Keros Therapeutics, Australia Pty Ltd.

The study also includes a **placebo** to match the ker-050 solution for injection, serving as the comparator treatment. The placebo is designed to mimic the appearance and administration route of elritercept, ensuring the study remains double-blind. The placebo is administered subcutaneously, following the same schedule as the experimental medication, to maintain consistency in the treatment protocol. The use of a placebo allows for the assessment of elritercept's efficacy and safety in reducing red blood cell transfusions in participants with transfusion-dependent anemia associated with very low-, low-, or intermediate-risk myelodysplastic syndromes.

The efficacy of **elritercept** in the clinical trial will be assessed primarily by evaluating the proportion of participants achieving transfusion independence (TI) for at least 8 weeks from baseline through week 24. This primary endpoint is designed to measure the reduction in red blood cell (RBC) transfusions among participants with transfusion-dependent anemia associated with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS).

Secondary endpoints include the proportion of participants achieving TI for at least 24 weeks from baseline through week 48, the proportion of participants with high transfusion burden (HTB) achieving TI for at least 8 weeks from baseline through week 24, and the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Additionally, changes from baseline in clinical laboratory values, vital signs, and electrocardiograms (ECGs) will be monitored to further assess the efficacy and safety of the treatment.