A Study to Evaluate the Safety and Effectiveness of Luspatercept for the Treatment of Transfusion-dependent (TD) Anemia Associated With Myelodysplastic Syndromes (MDS) & Beta-thalassemia (β-Thal) in India

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of luspatercept in participants who require regular blood cell transfusions due to b-thalassemia and myelodysplastic syndromes in India

Official Title
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A Phase 4 Study to Evaluate Safety and Effectiveness of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic SyndromeS (MDS) With Ring Sideroblasts Who Require Red Blood Cell Transfusions in Subjects Who Have Had Unsatisfactory Response to or Are Ineligible to Erythropoietin Based Therapy and in Subjects With Transfusion Dependent Anemia Due to Beta-Thalassemia

Conditions
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Anemia

Intervention / Treatment
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* Biological: Luspatercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: β-Thalassemia Cohort Documented diagnosis of β-thalassemia or hemoglobin (Hb E/β-thalassemia). (β-thalassemia with mutation and/or multiplication of alpha [α] globin is allowed). Regularly transfused, defined as 6 RBC units to 20 RBC units in the 24 weeks prior to enrollment and no transfusion-free period for > 35 days during that period. MDS-RS Cohort - Participant has documented diagnosis of MDS according to World Health Organization (WHO) (2016)/French-American-British FAB classification that meets revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease and the following criteria: i) RS ≥ 15% of erythroid precursors in bone marrow. If the SF3B1 mutation is present, RS ≥ 5% will be included. ii) Less than 5% blasts in bone marrow and < 1% peripheral blood blasts. iii) Peripheral blood white blood cell (WBC) count < 13,000/ microliters (μL). If the participant was previously treated with erythropoiesis-stimulating agents (ESAs) or granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), both agents must have been discontinued ≥ 4 weeks prior to the date of enrollment. Exclusion Criteria: β-Thalassemia Cohort A diagnosis of Hb S/β-thalassemia or α-thalassemia (for exampe, Hemoglobin H). Deep vein thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to enrollment. Use of chronic anticoagulant therapy is excluded unless the treatment stopped at least 28 days prior to enrollment. Anticoagulant therapies used for prophylaxis for surgery or high-risk procedures as well as low-molecular-weight (LMW) heparin for superficial venous thrombosis and chronic aspirin are allowed. MDS-RS Cohort MDS associated with del 5q cytogenetic abnormality. Secondary MDS, that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases. Participant has known clinically significant anemia due to iron, vitamin B12, or folate deficiencies; autoimmune or hereditary hemolytic anemia; or gastrointestinal bleeding. Iron deficiency to be determined by serum ferritin ≤ 15 micrograms per liter (μg/L) and additional testing if clinically indicated (for example, calculated transferrin saturation [iron/total iron binding capacity ≤ 20%] or bone marrow aspirate [BMA] stain for iron).

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Luspatercept<br> | Biological: Luspatercept<br>* Specified dose on specified days<br>* Other names: BMS-986346;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| β-Thal Cohort: Number of participants with treatment-related adverse events (AEs) of grade 3 or higher |  | Up to 57 weeks | 
| MDS-Ring Sideroblasts (RS) Cohort: Number of participants with treatment-related AEs of grade 3 or higher |  | Up to 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| β-Thal Cohort: Percentage of participants who achieved red blood cell (RBC) transfusion burden reduction (≥ 33% reduction from baseline) with a reduction of at least 2 red cell units |  | Week 13 to week 24 | 
| β-Thal Cohort: Percentage of participants who achieved RBC transfusion burden reduction of at least 33% from baseline during any 12-week interval with a reduction of at least 2 red cell units |  | Up to 57 weeks | 
| MDS-RS Cohort: Percentage of participants who achieved RBC-TI during any consecutive 56-day period |  | Week 1 to week 24 | 
| β-Thal Cohort: Number of participants with treatment-related AEs |  | Up to 57 weeks | 
| MDS-RS Cohort: Number of participants with treatment-related AEs |  | Up to 54 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Luspatercept, ACE-536, Transfusion dependent, Beta-thalassemia, Myelodysplastic syndromes with ring sideroblasts, Anemia, Hemoglobinopathies, Hematologic diseases, Bone marrow diseases