NCT05773729招募中不适用
Safety and Efficacy of Lentiviral Vector Transduction of β-globin Genetically Modified Autologous CD34+ Hematopoietic Stem Cells in Patients With Transfusion-dependent β-thalassemia
Shanghai BDgene Co., Ltd.1 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2023年9月15日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence (TI) for at least 6 months
研究概览
简要总结
This study will be intented to evaluate the safety, tolerability, and engraftment efficacy after myeloablative preconditioning and transplantation of autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the human βA-T87Q-globin gene in patients with transfusion-dependent (TDT) β-thalassemia.
详细描述
This is an open-label, single-dose study of BD211 in patients with transfusion-dependent β-thalassemia aged 3 to 18 years. It is estimated that 10 subjects will be enrolled. BD211 is a gene modified gene therapy product designed to produce healthy β-globin in red blood cells in beta-thalassemia patients. The total follow-up duration was 24 months, the safe endpoints and effectiveness endpoints will be used to assess the safety and efficacy profiles in patients with transfusion-dependent β-thalassemia.
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 3 to 18 years old, including:
- •The parents or legal guardians must be able to understand and provide ICFs. If available, it is strongly recommended that children aged ≥8 years in treatment decisions and obtain written ICFs and be clearly documented; Diagnosed as Transfusion Dependent β-thalassemia with any genotype (β0, β+, βE/β0, βS/S, βS/β0, βS/β+), confirmed the Hb analysis. No alfa chain genetic abnormalities. Subjects must stabilize and maintain an appropriate iron chelation regimen. Transfusion-dependent types are defined as requiring at least 100 mL/kg/ year of red blood cells (pRBCs).
- •No eligiblity for allogeneic hematopoietic stem cell transplantation.
- •The treatment of erythrocyte maturation agent luspatercept cannot be financially supported.
- •The subjects' parents/legal guardians must be willing and able to follow the study procedures in the study protocol.
- •Good organs' functions.
- •Having complete medical records including a history of blood transfusions testified subject received treatment and followed up for at least two years prior to screening .
排除标准
- •Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
- •HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
- •An active bacterial, viral, fungal or parasitic infection.
- •Contraindicated for the extraction of bone marrow under anesthesia.
- •Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
- •Peripheral blood white blood cell (WBC) count < 3×10^9/L or platelet count < 120×10^9/L.
- •A history of allo-transplantation.
- •Erythropoietin was used within 3 months prior to HSC cell collection.
- •Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
- •Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
- •Active recurrent malaria.
- •Had autoimmune diseases that may make blood transfusions difficult.
- •History of major organ injury including:
- •Liver disease, transaminase > 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction < 25%; Kidney disease, creatinine clearance < 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 * < 10 ms; Significant pulmonary hypertension needing clinical medical intervention.
- •There are bleeding diseases that have not been cured.
- •The subject involved with another clinical study in a 30-day screening period.
- •Allergic to the research drug and its excipients.
- •Prior treatment with any type of gene and/or cell therapy.
- •As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
- •Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
- •Had diseases that interfere with hematopoietic stem cells collections.
- •Any other conditions being ineligible for HSC transplantation determined by the investigator.
结局指标
主要结局
Percentage of treated participants with Transfusion-Dependent β-Thalassemia (TDT) who achieved transfusion independence (TI) for at least 6 months
时间窗: 24 months
TI defined as peripheral blood weighted average hemoglobin (Hb) \> or = 9 g/dL without packed red blood cell (pRBC) transfusion for 60 days after BD211 treatment, and transfusion is continuously halted for 12 months.
次要结局
- Hb (g/dL) level between 12 and 24 months after BD211 treatment compared with baseline Hb level(24 months)
- Measurement of PD/PK parameters(24 months)
- Neutrophil engraftment and platelet engraftment(24 months)
- Parameters of iron overload after BD211 treatment(24 months)
- Transplant-related mortality in 3 months and 12 months(12 months)
- Parameters of efficacy related to TI achievement after BD211 treatment(24 months)
- Change in quality of life from baseline(24 months)
- Parameters of efficacy related to reduced blood transfusion after BD211 treatment(24 months)
- Parameters of growth and development after BD211 treatment(24 months)
- Total hospitalizing days at 12, and 24 months (discharge after transplant)(24 months)
- RCL incidence(24 months)
- Frequency and severity of AE(24 months)
- Overall survival(24 months)
- Characterized insertion mutagenesis events that lead to clonal dominance or leukemia(24 months)
研究者
研究点 (1)
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