A Phase I/II Clinical Study Evaluating the Safety and Efficacy of KL003 Cell Injection in Transfusion-dependent Β-thalassemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- KL003 engraftment
研究概览
简要总结
This is a non-randomized, open label, single-dose study in up to 41 participants with β-thalassemia major. The goal of this clinical trial is to evaluate the safety and efficacy of KL003 cell injection in subjects with β-thalassemia major.
详细描述
This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess KL003 Cell Injection in up to 41 participants with transfusion-dependent β-thalassemia (TDT) who are ≥3 and ≤35 years of age. KL003 Cell Injection is autologous CD34+ stem cells transduced Ex Vivo with a lentiviral Vector encoding βA-T87Q-Globin.
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
- •Male or female age between 3-35 years;
- •Diagnosis of transfusion-dependent β-thalassemia and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years;
- •Karnofsky performance status ≥70 for participants≥16 years of age; Lansky performance status of ≥70 for participants<16 years of age;
- •Eligible to undergo auto-HSCT;
- •Willing and able to follow the research procedures and conditions, with good compliance;
- •Willing to receive at least the 2 years follow-up;
- •Participant and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form.
排除标准
- •Diagnosis of composite α thalassemia;
- •Prior receipt of gene therapy or allo-HSCT;
- •Meet the criteria for allo-HSCT and with an identified willing donor with full HLA match;
- •Participants with severe iron overload at the time of screening;
- •Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody;
- •Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.);
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator;
- •Subjects positive with the following etiological tests: human immunodeficiency virus(HIV-1-2),human cytomegalovirus (HCMV-DNA),EB virus（EBV-DNA）,HBV (HBsAg/HBV-DNA positive),HCV antibody (HCV-Ab), Human T-lymphotropic virus antibody (HTLV-Ab), Treponema pallidum antibody (TP-Ab);
- •Uncorrectable coagulation dysfunction or history of severe bleeding disorder;
- •History of major organ damage including:
- •Liver function test suggest AST or ALT levels >3× upper limit of normal（ULN）;
- •Total serum bilirubin value>2.5×ULN;if combined with Gilbert syndrome, total bilirubin>3×ULN and direct bilirubin value>2.5×ULN;
- •Left ventricular ejection fraction <45%;
- •Baseline calculated eGFR<60mL/min/1.73m2;
- •Pulmonary function:FEV1/FVC<60% and/or diffusion capacity of carbon monoxide (DLco) <60% of prediction;
研究组 & 干预措施
KL003 Cell Injection Drug Product
Transplant of auto-HSC transduced with lentiviral vector encoding βA-T87Q-globin gene
干预措施: KL003 Cell Injection Drug Product (Drug)
结局指标
主要结局
KL003 engraftment
时间窗: From time of KL003 infusion through Month 2
Proportion of participants with successful engraftment within 42 days after KL003 infusion.
Engraftment time of neutrophil and platelet
时间窗: From time of KL003 infusion through Month 24
Neutrophil engraftment was defined as the first day when neutrophils ≥ 0.5×10\^9/L for 3 consecutive days; Platelet engraftment was defined as the first the first day of platelet count ≥ 20.0×10\^9/L for 7 consecutive days with no platelet transfusions.
Overall Survival
时间窗: From time of KL003 infusion through Month 24
Overall survival was defined as time from date of KL003 infusion to date of death.
The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products
时间窗: From time of KL003 infusion through Month 24
Frequency and severity of AEs \& SAEs identified according to NCI CTCAE 5.0
Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation
时间窗: From time of KL003 infusion through Month 24
Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time
Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
时间窗: From time of KL003 infusion through Month 24
Peripheral blood samples were analyzed for detection of RCL
次要结局
- The proportion of participants achieved Transfusion Independence (TI)for at least 6 months(From time of KL003 infusion through Month 24)
- The proportion of participants achieved TI 12(From time of KL003 infusion through Month 24)
- The start time of Transfusion Independence (TI) after KL003 infusion(From time of KL003 infusion through Month 24)
- Total Hb and the vector-derived HbA^T87Q(From time of KL003 infusion through Month 24)