A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of luspatercept (ACE-536) for the treatment of anemia due to Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) in Chinese and Japanese participants with ring sideroblasts who require Red Blood Cells (RBC) transfusions.

Official Title
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A Phase 2, Multicenter, Single-Arm Bridging Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes(MDS) in Chinese and Japanese Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Luspatercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory or intolerant to, or ineligible for, prior Erythropoiesis stimulating agent (ESA) treatment as defined by any one of the following: Refractory to prior ESA treatment, Intolerant to prior ESA treatment, or ESA ineligible. previously treated with an ESA or granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, both agents must have been discontinued ≥ 4 weeks prior to date of luspatercept treatment Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 Exclusion Criteria: Prior therapy with disease modifying agents for underlying MDS disease Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Luspatercept Administration<br> | Drug: Luspatercept<br>* Specified dose on specified days<br>* Other names: ACE-536;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks |  | Week 1 through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC-TI ≥ 12 weeks |  | Week 1 through Week 24 | 
| Reduction in Red Blood Cell (RBC) units transfused over 16 weeks compared to baseline |  | Week 9 through Week 24 | 
| Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG) |  | Week 1 through Week 24 | 
| Mean hemoglobin increase ≥ 1.0 g/dL |  | Week 1 through Week 24 | 
| Duration of RBC-TI |  | Week 1 through Week 24 | 
| Mean decrease in serum ferritin compared to baseline |  | Week 9 through Week 24 | 
| Mean decrease in iron chelation therapy (ICT) use compared to baseline |  | Week 9 through Week 24 | 
| Time to RBC-TI |  | Week 1 through Week 24 | 
| Progression to acute myeloid leukemia (AML) |  | Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose | 
| Overall survival (OS) |  | Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose | 
| Incidence of type of adverse events (AEs) |  | Screening through 42 days post last dose | 
| Incidence of frequency of AEs |  | Screening through 42 days post last dose | 
| Incidence of severity of AEs |  | Screening through 42 days post last dose | 
| Incidence of seriousness of AEs |  | Screening through 42 days post last dose | 
| Incidence of relationship of AEs to study treatment |  | Screening through 42 days post last dose | 
| Pharmacokinetics - Area under the curve (AUC) |  | Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose | 
| Pharmacokinetics - Maximum plasma concentration of the drug (Cmax) |  | Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose | 
| Frequency of Anti-drug antibodies (ADA) |  | Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, MDS, ACE-536, Anemia, Luspatercept