A Phase 1/2 Clinical Study to Evaluate the Safety and Efficacy of Single Dose Intravenous Infusion of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 39
- 试验地点
- 11
- 主要终点
- Proportion of stem cell engrafted subjects
研究概览
简要总结
This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in subjects with Transfusion-Dependent β-Thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)
详细描述
This clinical trial is a multi-center, single-arm, single-dose, open-label study without dose escalation. The proposed dose is ≥ 3 × 106 CD34 + cells/kg administered as a single intravenous infusion. The primary objective of Phase 1 is to explore the safety of the study drug in different age groups. For subjects of each age group, myeloablative conditioning and dosing of the remaining subjects was initiated only after completion of dosing and safety observations and assessments in sentinel subjects. The Phase 2 primary objective was to determine the effectiveness of BRL-101 administered intravenously to patients with TDT.
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 HIV, TP, HBV, HCV, CMV and EBV.
- •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.
- •Prior hematopoietic stem cell transplant (HSCT).
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
BRL-101
BRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of BRL-101.
干预措施: BRL-101 (Drug)
结局指标
主要结局
Proportion of stem cell engrafted subjects
时间窗: Within 42 Days After BRL-101 Infusion
Stem cell engraftment was defined as an absolute peripheral blood neutrophil count of ≥ 0.5 × 109/L for 3 consecutive days within 42 days following BRL-101 intravenous infusion.
Time to neutrophil engraftment
时间窗: Up to 12 Months After BRL-101 Infusion
Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days
Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion
时间窗: Up to 12 Months After BRL-101 Infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
次要结局
未报告次要终点