β-thalassemia is one of the most common inherited hemoglobinopathies worldwide and a major public health issue that severely impacts birth quality, human health, and social progress. Currently, there are limited clinical drugs specifically designed to treat patients with β-thalassemia. This clinical trial aims to evaluate the efficacy and safety of luspatercept combined with low-dose thalidomide compared with luspatercept alone in patients with thalassemia. Key questions to be answered include: * Does luspatercept combined with low-dose thalidomide reduce the transfusion burden in patients with β-thalassemia major? * What medical problems may occur when patients receive luspatercept combined with low-dose thalidomide? In this clinical trial, participants were randomly assigned in a 1:1 ratio to either an intervention group (luspatercept combined with low-dose thalidomide) or a control group (luspatercept combined with placebo) using a central randomization system. The clinical efficacy and safety of the two groups were evaluated. The primary outcome measure was the clinical efficacy of luspatercept combined with low-dose thalidomide in reducing the transfusion burden in patients with β-thalassemia major.
This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the clinical efficacy and safety of luspatercept combined with low-dose thalidomide versus luspatercept combined with placebo in adult patients with β-thalassemia requiring regular red blood cell transfusions. The study is divided into the following phases: screening/run-in period, double-blind treatment period, and follow-up period. Participants are centrally randomized in a 1:1 ratio to either the intervention group or the control group. The primary objective is to compare the clinical response rate between the intervention group (luspatercept combined with low-dose thalidomide) and the control group (luspatercept combined with placebo) in adult patients with transfusion-dependent β-thalassemia. Clinical response is defined as the proportion of subjects achieving a reduction in red blood cell (RBC) transfusion burden by ≥50% and at least 2 units during weeks 13-24 after randomization compared with the baseline period (12 weeks prior to randomization). Secondary objectives mainly include assessments of other clinical efficacy indicators, iron metabolism, hemolysis, as well as the incidence of adverse events. Statistical analyses in this clinical study are based on the Intention-To-Treat (ITT) principle. Subgroup analyses of the primary endpoint are planned according to baseline transfusion burden (low, medium, and high transfusion burden groups). The study plans to consecutively enroll 78 participants across eight research centers: the First Affiliated Hospital of Guangxi Medical University, Liuzhou People's Hospital, Liuzhou Worker's Hospital, Yulin First People's Hospital, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise People's Hospital,Yunnan Provincial First People's Hospital and Southern Medical University Shenzhen Hospital. During the screening and run-in period, patients with severe β-thalassemia major (β-TM) who are scheduled to receive luspatercept combined with low-dose thalidomide or luspatercept monotherapy are invited to participate. Written informed consent is provided to potential subjects, along with a detailed explanation of the study content. Written informed consent from the subject (or their legal representative) must be obtained before any study-specific procedures are conducted. After signing the informed consent form, baseline data are collected. During the double-blind treatment period, the intervention group receives luspatercept combined with low-dose thalidomide, while the control group receives luspatercept combined with placebo. Both groups may receive best supportive care, including RBC transfusions, iron chelators, antiplatelet therapy, antibiotic therapy, antiviral and antifungal therapy, and/or nutritional support as needed. During the follow-up period, subjects are followed up at weeks 12, 24, 36, and 48. Data on physical examination, vital signs, hematological tests, clinical biochemistry, transfusion status, iron parameters, quality of life, concomitant treatments, subject compliance, and adverse events are collected and recorded in detail for further analysis of clinical efficacy and safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
78
The intervention group was treated with Luspatercept (starting dose level 1.0 mg/kg, once every 21 days) combined with low-dose thalidomide (starting dose level 50 mg/d) for 48 weeks.
The control group was treated with Luspatercept (starting dose level 1.0 mg/kg every 21 days) plus placebo (starting dose level 50 mg/d) for 48 weeks.
Southern Medical University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGAffiliated Hospital of Youjiang Medical College for Nationalities
Baise City, Guangxi, China
RECRUITINGBaise People's Hospital
Baise City, Guangxi, China
RECRUITINGLiuzhou People's Hospital
Liuchow, Guangxi, China
RECRUITINGLiuzhou Workers' Hospital
Liuchow, Guangxi, China
RECRUITINGYulin First People's Hospital
Yulin, Guangxi, China
RECRUITINGYunnan Provincial First People's Hospital
Kunming, Yunnan, China
RECRUITINGThe First Affiliated Hospital of Guangxi Medical University
Naning, China
RECRUITINGPercentage of Participants Who Achieved Erythroid Response - Week 13 to Week 24
Percentage of participants with a ≥50% reduction in RBC transfusion burden compared to baseline (RBC transfusion burden during the 12 weeks before randomization) and a reduction of at least 2 units for 12 consecutive weeks between Weeks 13 and 24 after randomization
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24
Percentage of Participants Who Achieved ≥ 50% And a Reduction of ≥ 2 RBC units From Baseline in Transfusion Burden- Week 37 to Week 48
Percentage of participants who achieved a ≥50% reduction in RBC transfusion burden relative to baseline, with a reduction of ≥ 2 RBC units, for 12 consecutive weeks between 37 and 48 weeks after randomization.
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48
Percentage Of Participants Who Achieved ≥ 33% And a Reduction of ≥ 2 RBC units Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Percentage Of participants who achieved a ≥33% reduction in RBC transfusion burden relative to baseline, with a reduction of ≥ 2 RBC units, for 12 consecutive weeks between 37 and 48 weeks after randomization.
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48
Percentage Of Participants Who Achieved ≥ 50% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48
Percentage Of participants who achieved a ≥50% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) for any consecutive 12 weeks (weeks 1-12, 13-24, 25-36, 37-48).
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48
Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - weeks 1-12, 13-24, 25-36, 37-48
Percentage Of participants who achieved a ≥33% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) for any consecutive 12 weeks (weeks 1-12, 13-24, 25-36, 37-48).
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48
Percentage Of Participants Who Achieved ≥ 50% Reduction From Baseline in Transfusion Burden - weeks 1-24, 25-48
Percentage Of participants with a ≥50% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) during any 24 consecutive weeks (weeks 1-24, 25-48);
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-24, 25-48
Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - weeks 1-24, 25-48
Percentage Of participants with a ≥33% reduction in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) during any 24 consecutive weeks (weeks 1-24, 25-48);
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-24, 25-48
Maximum percentage change in transfusion burden from baseline over 12 consecutive weeks
Percentage Of participants change in RBC transfusion burden relative to baseline (RBC transfusion burden during the 12 weeks prior to randomization) during any 12 consecutive weeks (weeks 1-12, 13-24, 25-36, 37-48);
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48
Percentage of Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks
Percentage of Participants who became transfusion-independent during any 8 consecutive weeks (weeks 1-8, 9-16, 17-24, 25-32, 33-40, 41-48);
Time frame: weeks 1-8, 9-16, 17-24, 25-32, 33-40, 41-48
Percentage of Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥12 Weeks
Percentage of Participants who became transfusion-independent during any 12 consecutive weeks (weeks 1-12, 13-24, 25-36, and 37-48);
Time frame: weeks 1-12, 13-24, 25-36, and 37-48
Maximum percentage change from baseline in the number of transfusion events over 12 consecutive weeks
Maximum percentage change from baseline in the number of transfusion events (RBC transfusion burden during the 12 weeks prior to randomization) during any 12 consecutive weeks (weeks 1-12, 13-24, 25-36, and 37-48);
Time frame: Baseline: Day -83 to Day 1; Treatment: Weeks1-12, 13-24, 25-36, 37-48
Concentration Change From Baseline to End of Treatment in serum ferritin
Concentration change from baseline in serum ferritin at weeks 12, 24, 36, and 48 after randomization;
Time frame: Baseline (prior to first dose of study drug) and Treatment (weeks 12,24,36,48)
Change From Baseline to End of Treatment in Iron deposition in organs
Change from baseline in myocardial iron and liver iron concentrations at weeks 24 and 48 after randomization;
Time frame: Baseline (prior to first dose of study drug) and Treatment (weeks 24,48)
Change From Baseline to End of Treatment in the average daily dose of iron chelation therapy
Change from baseline in the average daily dose of iron chelation therapy (ICT) during the treatment period (up to 48 weeks);
Time frame: Baseline (prior to first dose of study drug) and Treatment (weeks 1-48)
Change from baseline in self-reported Health-related quality-of-life (HRQoL) assessed by TranQoL
The TranQol is a self-administered quality of life tool developed for beta-thalassemia patients. The adult self-report version used in this study, includes 36 questions assessed on a 5-point response, that are grouped into 5 domains (Physical Health, Emotional Health, Sexual Health, Family Functioning, School/Career Functioning). Scores are calculated according to specific scoring algorithms developed by the authors. Both individual domains score and the total score range from 0 (worst) to 100 (best). Total Score and Physical Health domain score are reported. Positive change from baseline values indicate improvement.
Time frame: Baseline (prior to first dose of study drug) and Treatment (weeks 24,48)
Change from baseline in self-reported Health-related quality-of-life (HRQoL) assessed by SF-36
The SF-36 (version 2) is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. The raw score for each health domain is transformed into a 0 (worst) to 100 (best) domain score. The 0-100 scale score for each health domain is further converted to normbased scores using a T-score transformation, with a mean of 50 and a standard deviation (SD) of 10. Higher norm-based T-scores indicate better heath/QoL. The domains/summaries reported are: 1. Physical Functioning (Range of possible T-scores is 19.26 - 57.54) 2. General Health (Range of possible T-scores is 18.95 - 66.50) 3. Physical Component summary (PCS) (Range of possible T-scores is 5.02 - 79.78). Positive change from baseline values indicate improvement.
Time frame: Baseline (prior to first dose of study drug) and Treatment (weeks 24,48)
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