Clinical trial NCT05567458: A Study to Evaluate Luspatercept (ACE-536) in Chinese Participants Who Require Regular Red Blood Cell Transfusions Due to Beta (β)-Thalassemia.
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Beta-thalassemia
Keywords: Luspatercept
ACE-536
Transfusion burden
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants with ≥ 33% reduction from baseline in red blood cell (RBC) transfusion burden over any consecutive 24 weeks
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 - Week 48
Secondary outcomes:
measure: 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.
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
measure: Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 12 weeks
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over any consecutive 24 weeks
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 134
measure: Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 13-24
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 13-Week 24
measure: Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 37-48
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
measure: Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 1-24
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
measure: Proportion of participants with ≥ 33% reduction from baseline in RBC transfusion burden over Weeks 25-48
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 13-24
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 13-Week 24
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 37-48
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 1-24
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
measure: Proportion of participants with ≥ 50% reduction from baseline in RBC transfusion burden over Weeks 25-48
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
measure: Best change from baseline in total RBC units transfused in 24 weeks within the first 48-week treatment period
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 48
measure: Change from baseline in total RBC units transfused over Weeks 1-24
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 24
measure: Change from baseline in total RBC units transfused over Weeks 25-48
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 25 to Week 48
measure: Mean change from baseline in serum ferritin
timeFrame: 12 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
measure: Change from baseline in Liver Iron Concentration (LIC) (mg/g dw) by magnetic resonance imaging (MRI)
timeFrame: Up to 96 weeks
measure: Change from baseline in myocardial iron by T2-star (T2*) MRI
timeFrame: Up to 96 weeks
measure: Change from baseline in mean daily dose of iron chelation therapy (ICT)
timeFrame: 12 weeks prior to Dose 1 Day 1 (inclusive); Week 37 to Week 48
measure: Change from baseline in self-reported Health-related quality-of-life (HRQoL) assessed by TranQoL
timeFrame: Up to 48 weeks
measure: Change from baseline in self-reported HRQoL assessed by SF-36
timeFrame: Up to 48 weeks
measure: Proportion of participants who are transfusion independent for any consecutive ≥8 weeks during treatment
timeFrame: Week 1 to Week 134
measure: Proportion of participants who are transfusion independent for any consecutive ≥12 weeks during treatment
timeFrame: Week 1 to Week 134
measure: Duration of reduction in transfusion burden
timeFrame: Week 1 to Week 134
measure: Duration of RBC transfusion independence (TI)
timeFrame: Week 1 to Week 134
measure: Time to response
timeFrame: Week 1 to Week 134
measure: Least number of transfusion events in 24 weeks within the first 48-week treatment period
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Week 1 to Week 48
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to 4 years
measure: Frequency of Antidrug antibodies (ADA)
timeFrame: Up to 2 years
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 2 years
measure: Area under the curve (AUC)
timeFrame: Up to 2 years
measure: Change in spleen volume
timeFrame: Up to 96 weeks
measure: 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
timeFrame: 24 weeks prior to Dose 1 Day 1 (inclusive); Dose 1 Day 2 through completion of 48-week treatment for last subject
Other outcomes:
Locations:
city: Maoming
country: China
facility: Local Institution - 0002
state: Guangdong
city: Shenzhen
country: China
facility: Local Institution - 0005
state: Guangdong
city: Liuzhou
country: China
facility: Local Institution - 0007
state: Guangxi
city: Nanning
country: China
facility: Local Institution - 0003
state: Guangxi
city: Haikou
country: China
facility: Local Institution - 0006
state: Hainan
city: Kunming
country: China
facility: Local Institution - 0010
state: Yunnan
city: Guangzhou
country: China
facility: Local Institution - 0009
city: Guangzhou
country: China
facility: Local Institution - 0004
city: Haikou
country: China
facility: Local Institution - 0008
city: Nanning
country: China
facility: Local Institution - 0001
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: