A Phase 1/2/3 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Successful neutrophil engraftment
研究概览
简要总结
Evaluate the safety and efficacy of a single dose of autologous CRISPR Cas9 modified CD34⁺ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in subjects with severe sickle cell disease (SCD)
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of severe sickle cell disease
- •Documented severe sickle cell disease genotype
- •History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment
- •Eligible for autologous stem cell transplant as per investigators judgment
排除标准
- •An available 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
结局指标
主要结局
Successful neutrophil engraftment
Successful neutrophil engraftment
Time to neutrophil engraftment
Time to neutrophil engraftment
Time to platelet engraftment
Time to platelet engraftment
Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, and vital signs
Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, and vital signs
Transplant-related mortality (TRM) within 100 days after CTX001 infusion
Transplant-related mortality (TRM) within 100 days after CTX001 infusion
TRM within 1 year after CTX001 infusion
TRM within 1 year after CTX001 infusion
All-cause mortality
All-cause mortality
Proportion of subjects who have not experienced any severe VOC for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after last RBC transfusion for posttransplant support or SCD disease management
Proportion of subjects who have not experienced any severe VOC for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after last RBC transfusion for posttransplant support or SCD disease management
次要结局
- Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12) after CTX001 infusion. The evaluation of HF12 starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
- Proportion of subjects with reduction in annualized rate of severe VOCs at the time of analysis from baseline by at least 90%, 80%, 75%, 50% up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
- Relative change from baseline in annualized rate of severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
- Duration of severe VOC free in subjects who have achieved VF12
- Relative change from baseline in rate of inpatient hospitalizations for severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
- Relative change from baseline in annualized duration of hospitalization for severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
- Proportion of subjects with sustained HbF ≥20% at the time of analysis for at least 3 months, 6 months, or 12 months. The evaluation starts 60 days after last RBC transfusion for posttransplant support or SCD disease management
- Change in number of units of RBCs transfused for SCD-related indications over time
- HbF concentrations over time
- Hemoglobin (Hb) concentrations over time
- Change from baseline in reticulocyte count (percent reticulocytes and absolute reticulocyte count) over time
- Change from baseline in indirect bilirubin over time
- Change from baseline in haptoglobin over time
- Change from baseline in lactate dehydrogenase over time
- Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
- Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time
- Change in patient reported outcomes (PROs) over time in adults (≥18 years) using; - Pain-scale: 11-point numerical rating scale (NRS) - Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) - Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) - EuroQol Quality of Life Scale (EQ-5D-5L)
- Change in PROs over time in adolescents (12 to <18 years of age) using; - Pain-scale: 11-point NRS - Pediatric Quality of Life Inventory (PedsQL Teen selfreport and parent proxy versions) - PedsQL SCD module (Teen self-report and parent proxy versions) - EQ-5D-Youth (EQ-5D-Y self-report and parent proxy version)
研究者
Clinical Trials and Medical Info
Scientific
Vertex Pharmaceuticals Inc.