An Open Label Study Evaluating the Safety and Efficacy of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 6
- 主要终点
- achieve transfusion independence (TI)for at least ≥12 months after HGI-001 Injection infusion
研究概览
简要总结
Thalassemia is a group of recessively inherited hemoglobin disorders characterized by reduced or no production of hemoglobin and chronic anemia of varying severity. Severe β-thalassemia is transfusion-dependent thalassemia (TDT) and requires life-long transfusion, iron overload is a common complication of TDT. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option currently available for TDT, but it carries significant acute and long-term risks. In this study, the autologous HSCT-based gene therapy (referred to as "gene therapy for thalassemia, " by using HGI-001) is based on the principle that the autologous haemopoietic stem cells (HSCs) collected from the patient him/herself are transduced outside human body, which will restore the function of RBCs, so as to achieve the effect of treating or even curing thalassemia. Currently data suggests that gene therapy for TDT patients has shown remarkable therapeutic effects, avoiding immune rejection, and is widely accepted by the medical community, positioning it as a highly promising treatment approach. To date, the efficacy and safety of HGI-001 have been evaluated through both in vitro and in vivo studies. In an early-phase clinical study of HGI-001 conducted in China, five patients achieved transfusion-independent post-treatment. Among them, four have maintained this state for over two years, with the longest duration reaching 3.5 years. The study noted no severe adverse events. The long-term safety and efficacy of HGI-001 continue to be under active surveillance.
详细描述
This is a single-arm, open-label, single-dose, single site study in approximately 6 subjects ≥12 and ≤45 years of age with TDT. Subjects must have TDT with a transfusion history of at least 100mL/kg/year of packed red blood cells (pRBCs) or 8 transfusions of pRBCs per year in the past 2 years before enrollment.
Stage 1: Screening to determine eligibility for treatment: Subjects with previously known β0/β0 or non-β0/β0 genotypes are eligible for screening.
Stage 2: Autologous CD34+ cell collection, HGI-001 Injection manufacture and disposition: Each subject will undergo HSC mobilization with a granulocyte-colony stimulating factor (G-CSF) and plerixafor. Peripheral blood mononuclear cells (PBMCs) will be collected by apheresis. A total of 2 mobilization cycles may be performed if needed and each mobilization cycle may include up to 3 days for apheresis.
Stage 3: Myeloablative conditioning and infusion of HGI-001 Injection (Day 0)
: the subject will undergo myeloablative conditioning with busulfan. After completion of the 4-day course of busulfan, there must be a minimum of 48 hours of washout period before administration of HGI-001 Injection. On study Day 0, after thawing, the HGI-001 Injection will be administered via intravenous (IV) infusion at a dose of >4.0 × 106 CD34+ cells/kg.
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
- 12 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects between 12 and 45 years of age at the time of consent and are able to provide written informed consent.
- •Diagnosis of TDT, also known as β-thalassemia major, without genotype restriction, and a valid test report can be provided.
- •A history of at least 100 mL/kg/year of pRBCs transfusion or ≥ 8 transfusions of pRBCs per year for previous 2 years.
- •Sufficient blood transfusion for at least 3 months before screening (transfusion records can be provided), and Hb is maintained ≥9.0 g/dL before each transfusion.
- •The level of ferritin <5000ng/mL; Cardiac magnetic resonance imaging (MRI) T2 and liver MRI T2 findings suggest iron overload at a moderate level or below.
- •Clinically stable, and eligible for autologous hematopoietic stem cell transplant (auto-HSCT).
- •Adequate organ function for the conditioning with busulfan.
排除标准
- •Uncorrected bleeding disorder;
- •Uncontrolled epilepsy or mental disorders;
- •Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
- •Usage of psychoactive substance, drug, or alcohol abuse within six months prior to screening.
- •Pulmonary hypertension without effective intervention.
- •Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment.
- •Positive for anti-RBC antibodies.
- •Positive for hepatitis B surface antigen (HBsAg) and HBV DNA copy number > upper limit of normal (ULN) (HBV DNA test not required for patients negative for HBsAg), positive for hepatitis C virus (HCV) antibody, unless HCV RNA is negative (HCV RNA-negative subjects are not excluded), positive human immunodeficiency virus (HIV), or positive for Treponema pallidum antibody (TP-Ab) (subjects who are positive for the antibody due to vaccination can be enrolled).
- •Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection.
结局指标
主要结局
achieve transfusion independence (TI)for at least ≥12 months after HGI-001 Injection infusion
时间窗: 12 month after injection of study drug
Subjects achieve transfusion independence (TI), which is defined as a weighted average Hb ≥9 g/dL without any pRBC transfusions at any time for a continuous period of ≥12 months during the study after HGI-001 Injection infusion
次要结局
未报告次要终点
研究者
Chi Kong Li
Professor
Prince of Wales Hospital, Shatin, Hong Kong