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临床试验/NCT05773729
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

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

发起方
Shanghai BDgene Co., Ltd.
申办方类型
Industry
责任方
Sponsor

研究点 (1)

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