an Open Label Trial of Evaluation of the Safety and Efficacy of Treatment With γ-globin Reactivated Autologous Hematopoietic Stem Cells in Subjects With β-thalassemia Major
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Time to platelet engraftment
研究概览
简要总结
This is a single arm, open label, single-dose, phase 1/2 study in up to 5 participants with β-thalassemia major.The study will evaluate the safety and efficacy of the treatment with γ-globin reactivated autologous hematopoietic stem cells in subjects with β-thalassemia major.
详细描述
γ-globin reactivated autologous hematopoietic stem cells will be manufactured using Glycosylase Base Editors. Subject participation for this study will be 2 year. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 15 years post-transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent.
- •Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+、β
- •+β0, βEβ0 genotype.
- •Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV.
- •Subjects body condition eligible for autologous stem cell transplant.
排除标准
- •Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor.
- •Active bacterial, viral, or fungal infection.
- •Treated with erythropoietin prior 3 months.
- •Immediate family member with any known hematological tumor.
- •Subjects with severe psychiatric disorders to be unable to cooperate.
- •Recently diagnosed as malaria.
- •History of complex autoimmune disease.
- •Persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 X the upper limit of normal (ULN).
- •Subjects with severe heart, lung and kidney diseases.
- •With serious iron overload, serum ferritin>5000mg/ml.
- •Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or Investigator.
- •Subjects who are receiving treatment from another clinical study, or have received another gene therapy.
- •Subjects or guardians had resisted the guidance of the attending doctor.
- •Subjects whom the investigators do not consider appropriate for participating in this clinical study
研究组 & 干预措施
γ-globin reactivated autologous hematopoietic stem cells
each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells
干预措施: γ-globin reactivated autologous hematopoietic stem cells (Biological)
结局指标
主要结局
Time to platelet engraftment
时间窗: From 12 months to 24 months post transplant
Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
时间窗: From 12 months to 24 months post transplant
Time to neutrophil engraftment
时间窗: From 12 months to 24 months post transplant
Frequency and severity of adverse events through 100 days after BRL-103 Infusion
时间窗: From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
时间窗: From 12 months to 24 months post transplant
TR3 was defined as at least a 50% reduction in monthly red blood cell transfusion volume and transfusion frequency compared to baseline for at least 3 months
次要结局
- Proportion of subjects achieving TR12(From 12 months to 24 months post transplant)
- Proportion of subjects achieving TR6(From 12 months to 24 months post transplant)
- Fetal hemoglobin concentration (pre-transfusion) over time(From 12 months to 24 months post transplant)
- Change in serum ferritin level from baseline over time(From 12 months to 24 months post transplant)
- Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)(From 12 months to 24 months post transplant)
- Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)(From 12 months to 24 months post transplant)
- Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time(From 12 months to 24 months post transplant)
- Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)(From 12 months to 24 months post transplant)
- Incidence of transplant related mortality (TRM) within 100 days and within 1 year(From 12 months to 24 months post transplant)
- Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.(From 12 months to 24 months post transplant)
- Total hemoglobin concentration (pre-transfusion) over time(From 12 months to 24 months post transplant)
- All-cause mortality(From 12 months to 24 months post transplant)