Evaluating the Clinical Efficacy and Safety of Luspatercept Combined With Thalidomide in the Treatment of β-TDT Patients

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.

• Percentage of Participants Who Achieved ≥ 50% And a Reduction of ≥ 2 RBC units From Baseline in Transfusion Burden- Week 37 to Week 48 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline: Day -83 to Day 1; Treatment: Weeks1-24, 25-48]
• Maximum percentage change in transfusion burden from baseline over 12 consecutive weeks [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline (prior to first dose of study drug) and Treatment (weeks 24,48)]