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: Recruiting
• Conditions: Beta-thalassemia
• Intervention / Treatment: Drug: Placebo; Drug: Luspatercept

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain the NCT# and Site#.
• Study Contact Backup: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• China
  • Guangzhou, China, 510515
    • Recruiting
    • Nanfang Hospital of Southern Medical University
    • Contact: Ling Jiang, Site 0004; Phone Number: +8613602791429
  • Guangzhou, China, 510120
    • Recruiting
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Contact: Danian Nie, Site 0009
  • Haikou, China, 570311
    • Recruiting
    • Hainan General Hospital
    • Contact: Guyun Wang, Site 0008; Phone Number: +8613006021266
  • Haikou, China, 570203
    • Recruiting
    • Hainan Medical College - First Affiliated Hospital
    • Contact: Shi Tao, Site 0006; Phone Number: +8618689559516
  • Liuzhou, China, 545006
    • Recruiting
    • Liuzhou General Hospital
    • Contact: Qin Liu, Site 0007; Phone Number: 8613978020485
  • Maoming, China, 525447
    • Recruiting
    • Maoming People's Hospital
    • Contact: Xiong Zhang, Site 0002; Phone Number: +8606682992967
  • Nanning, China, 530021
    • Recruiting
    • The First Affiliated Hospital of Guangxi Medical University
    • Contact: Yongrong Lai, Site 0001; Phone Number: +07715356746
  • Guangdong
    • Shenzhen, Guangdong, China, 518035
      • Recruiting
      • Shenzhen Second People's Hospital
      • Contact: Xin Du, Site 0005; Phone Number: 13602523722
  • Guangxi
    • Nanning, Guangxi, China, 530012
      • Recruiting
      • People's Liberation Army The 923rd Hospital
      • Contact: Xiaolin Yin, Site 0003; Phone Number: +8613321717899
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Recruiting
      • First People's Hospital of Yunnan Province
      • Contact: Yanmei Yang, Site 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.

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

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	Up to 48 weeks

Secondary Outcome Measures

Outcome Measure	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

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
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Estimated): February 3, 2025
• Study Completion (Estimated): July 2, 2025

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): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Luspatercept; ACE-536; Transfusion burden
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; 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: No
• Studies a U.S. FDA-regulated device product: No