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

Beta-thalassemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05567458
• Other study ID #: CA056-001
• Status: Recruiting
• Phase: Phase 2
• Start date: October 17, 2022
• Est. completion date: July 2, 2025

Study information

• Verified date: June 2024
• Source: Bristol-Myers Squibb
• Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: July 2, 2025
• Est. primary completion date: February 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-thalassemia or Hemoglobin E/ß-thalassemia (ß-thalassemia with mutation and/or multiplication of alpha (a) 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/ß-thalassemia or a-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

Related Conditions & MeSH terms

• Beta-thalassemia
• Thalassemia

Intervention

Drug:
• Luspatercept
Specified dose on specified days
• Placebo
Specified dose on specified days

Locations

Country	Name	City	State
China	Local Institution - 0004	Guangzhou
China	Local Institution - 0009	Guangzhou
China	Hainan General Hospital	Haikou
China	Hainan Medical College - First Affiliated Hospital	Haikou	Hainan
China	First People's Hospital of Yunnan Province	Kunming	Yunnan
China	Local Institution - 0011	Kunming	Yunnan
China	Local Institution - 0007	Liuzhou	Guangxi
China	Local Institution - 0002	Maoming	Guangdong
China	Local Institution - 0003	Nanning	Guangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean change from baseline in serum ferritin		12 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
Secondary	Change from baseline in Liver Iron Concentration (LIC) (mg/g dw) by magnetic resonance imaging (MRI)		Up to 96 weeks
Secondary	Change from baseline in myocardial iron by T2-star (T2*) MRI		Up to 96 weeks
Secondary	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
Secondary	Change from baseline in self-reported Health-related quality-of-life (HRQoL) assessed by TranQoL		Up to 48 weeks
Secondary	Change from baseline in self-reported HRQoL assessed by SF-36		Up to 48 weeks
Secondary	Proportion of participants who are transfusion independent for any consecutive =8 weeks during treatment		Week 1 to Week 134
Secondary	Proportion of participants who are transfusion independent for any consecutive =12 weeks during treatment		Week 1 to Week 134
Secondary	Duration of reduction in transfusion burden		Week 1 to Week 134
Secondary	Duration of RBC transfusion independence (TI)		Week 1 to Week 134
Secondary	Time to response		Week 1 to Week 134
Secondary	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
Secondary	Number of participants with Adverse Events (AEs)		Up to 4 years
Secondary	Frequency of Antidrug antibodies (ADA)		Up to 2 years
Secondary	Maximum plasma concentration (Cmax)		Up to 2 years
Secondary	Area under the curve (AUC)		Up to 2 years
Secondary	Change in spleen volume		Up to 96 weeks
Secondary	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

External Links

•   BMS Clinical Trial Information