NCT05444894进行中（未招募）1 期
A Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Dose of Autologous Clustered Regularly Interspaced Short Palindromic Repeats Gene-edited Cluster of Differentiation 34 (CD34+) Human Hematopoietic Stem and Progenitor Cells (HSPC) (EDIT-301) in Transfusion-Dependent Beta Thalassemia (TDT)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 9
- 试验地点
- 16
- 主要终点
- Proportion of participants achieving engraftment defined as neutrophil engraftment (defined as demonstrating absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L post EDIT-301 infusion for 3 consecutive measurements obtained on different days)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and efficacy of treatment with EDIT-301 in adult participants with Transfusion Dependent beta Thalassemia
详细描述
This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety, tolerability, and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant in adult participants with TDT, age 18 to 35 years, inclusive
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 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Transfusion Dependent B-Thalassemia as defined by:
- •Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and
- •History of at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to signing informed consent
- •Clinically stable and eligible to undergo autologous HSCT
- •Karnofsky Performance Status ≥ 70
排除标准
- •Available 10/10 human leukocyte antigen (HLA)-matched related donor
- •Prior HSCT or contraindications to autologous HSCT
- •Participants with associated a history of α-thalassemia and > 1 alpha chain deletion, or alpha multiplications as documented in medical records
- •Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records
- •Prior receipt of gene therapy
- •Inadequate bone marrow function, as defined by white blood cell count of < 3 x 10^9/L or a platelet count < 100 x 10^9/L (without hypersplenism), per investigator judgement
- •Inadequate organ function
- •Advanced liver disease
- •Any prior or current malignancy, or immunodeficiency disorder,
- •Immediate family member with a known or suspected Familial Cancer Syndrome
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection
结局指标
主要结局
Proportion of participants achieving engraftment defined as neutrophil engraftment (defined as demonstrating absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L post EDIT-301 infusion for 3 consecutive measurements obtained on different days)
时间窗: EDIT-301 infusion (Day 0) to 42 days post EDIT-301 infusion
Frequency and severity of adverse events (AEs) (incidence of AEs and Grade 3 or higher serious adverse events, using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.5.0)
时间窗: Screening through up to 24 months post EDIT-301 infusion
次要结局
- Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime(Baseline through up to 24 months post EDIT-301 infusion)
- Proportion of participants with hemoglobin concentration ≥ 9 g/dL(EDIT-301 infusion (Day 0) through 3, 6, 12 months up to 24 months post EDIT-301 infusion)
- Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time(EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion)
- Incidence of all-cause mortality(Screening through up to 24 months post EDIT-301 infusion)
- Proportion of alleles per participant with intended genetic modification present in peripheral blood over time(EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion)
- Change in the total hemoglobin concentration compared to baseline overtime(Baseline through up to 24 months post EDIT-301 infusion)
- Change in parameters of iron overload compared to baseline over time(Baseline through up to 24 months post EDIT-301 infusion)
- Kinetics of HSPC engraftment(EDIT-301 infusion (Day 0) to first day of 3 consecutive measurements of platelets ≥ 50 x 10^9/L for at least 1 week following the last platelet transfusion and 10 days following thrombopoietin mimetics use up to 24 months post EDIT-301 infusion.)
- Proportion of participants achieving the sustained transfusion reduction (TR) for at least 6 months and at least 12 months from 3 months post-EDIT-301 infusion(3 months post EDIT-301 infusion through up to 24 months post EDIT-301 infusion)
- Proportion of participants achieving the sustained transfusion independence (TI) for at least 6 months and, at least 12 months from 3 months post EDIT-301 infusion(3 months through up to 24 months post EDIT-301 infusion)
- Proportion of participants receiving iron chelation therapy over time(EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion)
- Incidence of transplant related mortality(EDIT-301 infusion (Day 0) through Day 100 post EDIT-301 infusion and from EDIT-301 infusion (Day 0) through 12 months post EDIT-301 infusion)
研究者
研究点 (16)
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