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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Beta-thalassemia
• Intervention / Treatment: Drug: Placebo; Drug: Luspatercept

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510120
    • Local Institution - 0009
  • Guangzhou, China, 510515
    • Local Institution - 0004
  • Haikou, China, 570311
    • Local Institution - 0008
  • Nanning, China, 530021
    • Local Institution - 0001
  • Guangdong
    • Maoming, Guangdong, China, 525447
      • Local Institution - 0002
    • Shenzhen, Guangdong, China, 518035
      • Local Institution - 0005
  • Guangxi
    • Liuzhou, Guangxi, China, 545006
      • Local Institution - 0007
    • Nanning, Guangxi, China, 530012
      • Local Institution - 0003
  • Hainan
    • Haikou, Hainan, China, 570203
      • Local Institution - 0006
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Local Institution - 0010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Participant who has EMH complications requiring treatment to control the growth of EMH mass(es) during the screening period.
• Participant used immunomodulatory imide drugs (IMiDs) ≤ 24 weeks prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Specified dose on specified days
Experimental: Luspatercept	Drug: Luspatercept; Specified dose on specified days; Other Names: ACE-536; BMS-986346

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with ≥ 33% reduction from baseline in red blood cell (RBC) transfusion burden over any consecutive 24 weeks	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 - Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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
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
Proportion of subjects with ≥ 33% reduction from baseline in RBC transfusion burden during any rolling 24-week interval compared to the 24-week interval prior to start of IP for luspatercept plus BSC versus placebo plus BSC.	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 24 weeks	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 13-24	24 weeks prior to Dose 1 Day 1 (inclusive); Week 13-Week 24
Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 37-48	24 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 1-24	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 25-48	24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 13-24	24 weeks prior to Dose 1 Day 1 (inclusive); Week 13-Week 24
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 37-48	24 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 1-24	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 25-48	24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
Best change from baseline in total RBC units transfused in 24 weeks within the first 48-week treatment period	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 48
Change from baseline in total RBC units transfused over Weeks 1-24	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
Change from baseline in total RBC units transfused over Weeks 25-48	24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
Mean change from baseline in serum ferritin	12 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
Change from baseline in mean daily dose of iron chelation therapy (ICT)	12 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
Proportion of participants who are transfusion independent for any consecutive ≥8 weeks during treatment	Week 1 to Week 134
Proportion of participants who are transfusion independent for any consecutive ≥12 weeks during treatment	Week 1 to Week 134
Duration of reduction in transfusion burden	Week 1 to Week 134
Duration of RBC transfusion independence (TI)	Week 1 to Week 134
Time to response	Week 1 to Week 134
Least number of transfusion events in 24 weeks within the first 48-week treatment period	24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 48
Number of participants with Adverse Events (AEs)	Up to 4 years
Proportion of subjects, without increase in transfusion burden and with an increase of ≥ 1.0 g/dL in pre-transfusion Hb level on at least 2 separate tests (at least 60 days apart) during any rolling 24-week interval, compared to baseline	24 weeks prior to Dose 1 Day 1 (inclusive); Dose 1 Day 2 through completion of 48-week treatment for last subject

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Luspatercept; ACE-536; Transfusion burden
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Hematinics; Luspatercept
• Other Study ID Numbers: CA056-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosurecommitment.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes