A Phase 1/2, Open-label, Single-arm Study to Assess the Safety, Tolerability, and Efficacy of ST-400 Autologous Hematopoietic Stem Cell Transplant for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 12
- 主要终点
- Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion
研究概览
简要总结
This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess ST-400 in 6 subjects with transfusion-dependent β-thalassemia (TDT) who are ≥18 and ≤40 years of age. ST-400 is a type of investigational therapy that consists of gene edited cells. ST-400 is composed of the patient's own blood stem cells which are genetically modified in the laboratory using Sangamo's zinc finger nuclease (ZFN) technology to disrupt a precise and specific sequence of the enhancer of the BCL11A gene (which normally suppresses fetal hemoglobin production in erythrocytes). This process is intended to boost fetal hemoglobin (HbF), which can substitute for reduced or absent adult (defective) hemoglobin. ST-400 is then infused back into the patient after receiving conditioning chemotherapy to make room for the new cells in the bone marrow, with the aim of producing new erythrocytes with increased amounts of HbF. The primary objective is to understand safety and tolerability of ST-400, and secondary objectives are to assess the effects on HbF levels and transfusion requirements.
详细描述
Once consented, study participants will progress through the following stages:
- Screening: in-person visit at the study site to confirm eligibility for proceeding
- Collection: autologous (self) blood stem cells are harvested at the study site, also known as apheresis
- Manufacturing of ST-400: no study participant activities expected
- Infusion: conditioning chemotherapy, followed by infusion of ST-400, occurs at the study site
- Follow-up: follow up at the study site to monitor for safety and effectiveness of the study
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
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent
- •Clinical diagnosis of TDT with ≥ 8 documented RBC transfusion events per year on an annualized basis in the 2-years prior to screening
- •Confirmed beta-thalassemia diagnosis by molecular genetic testing
- •Clinically stable and eligible to receive conditioning chemotherapy
- •Able and willing to use an effective method of contraception from the signing of the informed consent and for one year following ST-400 infusion.
排除标准
- •Previous history of autologous or allogeneic blood stem cell transplantation or solid organ transplantation
- •Pregnant or breastfeeding female
- •Medical contraindication to mobilization, apheresis, or conditioning
- •Significant liver, lung, heart, or kidney dysfunction
- •Diagnosis of HIV or evidence of active HBV or HCV
- •History of significant bleeding disorder or uncontrolled seizures
- •History of active malignancy in past 5 years (non-melanoma skin cancer or cervical cancer in situ permitted) any history of hematologic malignancy, or family history of cancer predisposition syndrome without negative testing result in the study candidate.
- •Currently participating in another clinical trial using an investigational study medication, or recent participation in such a trial
- •Previous treatment with gene therapy
结局指标
主要结局
Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion
时间窗: Up to 156 weeks after the ST-400 infusion
Safety and tolerability assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 weeks after the ST-400 infusion
次要结局
- Clinical Laboratory Measurements of Percent (%) HbF(Baseline, Weeks 26, 52, and 156 after ST-400 infusion)
- Clinical Laboratory Measurement of Hemoglobin (Hb) Fractions (A and F in g/dL)(Baseline, Weeks 26, 52, and 156 after ST-400 infusion)
- Annualized Frequency of Packed RBC Transfusions(From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion))
- Annualized Volume (mL) of Packed RBC Transfusions(From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion))