NCT05477563招募中3 期
A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Fetal Hemoglobin (HbF) Concentration Over Time
研究概览
简要总结
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.
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 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with TDT and SCD:
- •Eligible for autologous stem cell transplant as per investigator's judgment.
- •Participants with TDT:
- •Diagnosis of TDT as defined by:
- •Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning
- •History of at least 100 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
- •Participants with SCD:
- •Diagnosis of severe SCD as defined by:
- •Documented SCD genotypes
- •History of at least two severe VOCs events per year for the previous two years prior to enrollment
排除标准
- •Participants with TDT and SCD:
- •A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
- •Prior hematopoietic stem cell transplant (HSCT)
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
- •Participants with TDT:
- •Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
- •Participants with sickle cell β-thalassemia variant
- •Participants with SCD:
- •History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
CTX001
Experimental
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.
干预措施: CTX001 (Biological)
结局指标
主要结局
Fetal Hemoglobin (HbF) Concentration Over Time
时间窗: Up to 12 Months After CTX001 Infusion
Total Hemoglobin (Hb) Concentration Over Time
时间窗: Up to 12 Months After CTX001 Infusion
次要结局
- TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days)(Within 42 Days After CTX001 Infusion)
- TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time(Up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Haptoglobin(From Baseline up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Total Bilirubin(From Baseline up to 12 Months After CTX001 Infusion)
- TDT and SCD: Time to Engraftment(Up to 12 Months After CTX001 Infusion)
- TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions(From Day 60 up to 12 Months After CTX001 Infusion)
- TDT: Duration Transfusion Free in Participants(Up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs(From Baseline up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Indirect Bilirubin(From Baseline up to 12 Months After CTX001 Infusion)
- TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion(Within 100 Days After CTX001 Infusion)
- TDT and SCD: Incidence of All-cause Mortality(From Signing of Informed Consent up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)(From Baseline up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Lactate dehydrogenase(From Baseline up to 12 Months After CTX001 Infusion)
- TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion(Within 12 Months After CTX001 Infusion)
- TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time(Up to 12 Months After CTX001 Infusion)
- SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs(From Baseline up to 12 Months After CTX001 Infusion)
- TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Signing of Informed Consent up to 12 Months After CTX001 Infusion)
研究者
研究点 (6)
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