A Study to Evaluate Luspatercept (ACE-536) in Chinese Participants Who Require Regular Red Blood Cell Transfusions Due to Beta (β)-Thalassemia.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of luspatercept plus best supportive care (BSC) versus placebo plus BSC in participants who require regular red blood cell transfusions due to β-thalassemia.

Official Title
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A Phase 2, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Luspatercept (ACE-536) in Chinese Adult Subjects Who Require Regular Red Blood Cell Transfusions Due to Beta (β)-Thalassemia

Conditions
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Beta-thalassemia

Intervention / Treatment
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* Drug: Luspatercept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to adhere to the study visit schedule (for example, not scheduled to receive hematopoietic stem cell transplantation [HSCT]) and other protocol requirements. Participant has documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia (β-thalassemia with mutation and/or multiplication of alpha (α) globin is allowed). Participant is regularly transfused, defined as: 6-25 RBC units in the 24 weeks prior to randomization and no transfusion-free period for >42 days during that period. Participant has Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Exclusion Criteria: Participant has a diagnosis of Hemoglobin S/β-thalassemia or α-thalassemia (for example, Hemoglobin H). Participant has active hepatitis C virus (HCV) infection as demonstrated by a positive HCVribonucleic acid (RNA) test of sufficient sensitivity, or active infectious hepatitis B virus (HBV) as demonstrated by the presence of hepatitis B surface antigen (HBsAg) and/or HBVdeoxyribonucleic acid (DNA) positive, or known positive human immunodeficiency virus (HIV). Participant has a history of deep venous thrombosis or stroke or thromboembolic events (venous or arterial) requiring medical intervention ≤24 weeks prior to randomization. Participant uses chronic anticoagulant therapy, unless the treatment stopped at least 28 days prior to randomization. Anticoagulant therapies used for prophylaxis for surgery or high-risk procedures as well as low-molecular-weight heparin for superficial venous thrombosis and chronic aspirin are allowed.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with ≥ 33% reduction from baseline in red blood cell (RBC) transfusion burden over any consecutive 24 weeks |  | Up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks |  | Up to 48 weeks | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks |  | Up to 48 weeks | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 24 weeks |  | Up to 48 weeks | 
| Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 13-24 |  | Weeks 13 to 24 | 
| Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 37-48 |  | Weeks 37 to 48 | 
| Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 1-24 |  | Weeks 1 to 24 | 
| Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 25-48 |  | Weeks 25 to 48 | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 13-24 |  | Weeks 13 to 24 | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 37-48 |  | Weeks 37 to 48 | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 1-24 |  | Weeks 1 to 24 | 
| Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 25-48 |  | Weeks 25 to 48 | 
| Mean change from baseline in total RBC units transfused in 24 weeks within the first 48-week treatment period |  | Baseline up to Week 48 | 
| Change from baseline in total RBC units transfused over Weeks 1-24 |  | Baseline up to Week 24 | 
| Change from baseline in total RBC units transfused over Weeks 25-48 |  | Weeks 25 to 48 | 
| Mean change from baseline in serum ferritin |  | Baseline, Weeks 37 to 48 | 
| Change from baseline in Liver Iron Concentration (LIC) (mg/g dw) by magnetic resonance imaging (MRI) |  | Up to 96 weeks | 
| Change from baseline in myocardial iron by T2-star (T2*) MRI |  | Up to 96 weeks | 
| Change from baseline in mean daily dose of iron chelation therapy (ICT) |  | Baseline, Weeks 37 to 48 | 
| Change from baseline in self-reported Health-related quality-of-life (HRQoL) assessed by TranQoL |  | Up to 48 weeks | 
| Change from baseline in self-reported HRQoL assessed by SF-36 |  | Up to 48 weeks | 
| Proportion of participants who are transfusion independent for any consecutive ≥8 weeks during treatment |  | Up to 48 weeks | 
| Proportion of participants who are transfusion independent for any consecutive ≥12 weeks during treatment |  | Up to 48 weeks | 
| Duration of reduction in transfusion burden |  | Up to 48 weeks | 
| Duration of RBC transfusion independence (TI) |  | Up to 48 weeks | 
| Time to response |  | Up to 48 weeks | 
| Mean number of transfusion events in 24 weeks within the first 48-week treatment period |  | Baseline up to Week 48 | 
| Number of participants with Adverse Events (AEs) |  | Up to 48 weeks | 
| Frequency of Antidrug antibodies (ADA) |  | Up to 2 years | 
| Maximum plasma concentration (Cmax) |  | Up to 2 years | 
| Area under the curve (AUC) |  | Up to 2 years | 
| Change in spleen volume |  | Up to 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACE-536, Luspatercept, Transfusion burden