NCT05329649进行中（未招募）3 期
A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 13
- 试验地点
- 8
- 主要终点
- Proportion of Participants who do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)
研究概览
简要总结
This is a single-dose, open-label study in pediatric participants with severe SCD and hydroxyurea (HU) failure or intolerance. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (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
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Hydroxyurea (HU) failure unless HU intolerant
- •Eligible for autologous stem cell transplant as per investigators judgment
排除标准
- •A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor
- •Prior hematopoietic stem cell transplant (HSCT).
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection
- •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 single infusion of CTX001 through central venous catheter.
干预措施: CTX001 (Biological)
结局指标
主要结局
Proportion of Participants who do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)
时间窗: Up to 24 Months After CTX001 Infusion
次要结局
- Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time(Up to 24 Months After CTX001 Infusion)
- Duration of Severe VOC Free in Participants who Have Achieved VF12(Up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months(Up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months(Up to 24 Months After CTX001 Infusion)
- 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)
- Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)(Up to 24 Months After CTX001 Infusion)
- Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time(Up to 24 Months After CTX001 Infusion)
- Time to Engraftment(Up to 24 Months After CTX001 Infusion)
- Incidence of All-cause Mortality(From Signing of Informed Consent up to 24 Months After CTX001 Infusion)
- Relative Reduction in Annualized Rate of Severe VOCs(From Baseline up to 24 Months After CTX001 Infusion)
- Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs(From Baseline up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months(Up to 24 Months After CTX001 Infusion)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Signing of Informed Consent up to 24 Months After CTX001 Infusion)
- Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion(Within 100 Days After CTX001 infusion)
- Time for Participants to Reach HbF ≥20%(Up to 24 Months After CTX001 Infusion)
- Proportion of Participants with Detectable Haptoglobin Over Time(Up to 24 Months After CTX001 Infusion)
- Relative Reduction from Baseline in Annualized Volume and Episodes of RBC Transfusions for SCD-related indications starting after Month 12 post-CTX001 infusion(Up to 24 Months After CTX001 Infusion)
- Hemoglobin (Hb) Concentrations Over Time(Up to 24 Months After CTX001 Infusion)
- Incidence of TRM Within 12 Months After CTX001 Infusion(Within 12 Months After Infusion)
- Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs(From Baseline up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months(Up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months(Up to 24 Months After CTX001 Infusion)
- Time for Participants to Reach HbF ≥30%(Up to 24 Months After CTX001 Infusion)
- HbF Concentrations Over Time(Up to 24 Months After CTX001 Infusion)
- Change in Reticulocyte Count Over Time(From Baseline up to 24 Months After CTX001 Infusion)
- Change in Haptoglobin Over Time(From Baseline up to 24 Months After CTX001 Infusion)
- Proportion of Participants with Normalized LDH Over Time(Up to 24 Months After CTX001 Infusion)
- Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months(Up to 24 Months After CTX001 Infusion)
- Change in Indirect Bilirubin Over Time(From Baseline up to 24 Months After CTX001 Infusion)
- Change in Lactate Dehydrogenase (LDH) Over Time(From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion)
研究者
研究点 (8)
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