A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in subjects with Transfusion-Dependent β-Thalassemia
概览
- 阶段
- 3 期
- 干预措施
- 未指定
- 疾病 / 适应症
- 未指定
- 发起方
- Vertex Pharmaceuticals Inc.
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- All-cause mortality
- 状态
- 进行中（未招募）
- 最后更新
- 去年
概览
简要总结
To evaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ hHSPCs (CTX001) in subjects with TDT
研究者
Clinical Trials and Medical Info
Scientific
Vertex Pharmaceuticals Inc.
入排标准
入选标准
- •Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by: Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Subjects 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 mL/kg/year or ≥10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening.
- •Eligible for autologous stem cell transplant as per investigator's judgment.
排除标准
- •A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator's judgement.
- •Prior allo-HSCT.
- •Subjects with associated α-thalassemia and >1 alpha deletion or alpha multiplications.
- •Subjects with sickle cell beta thalassemia variant.
- •Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
- •White blood cell (WBC) count <3 × 10^9/L or platelet count <50 × 10^9/L not related to hypersplenism.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
结局指标
主要结局
All-cause mortality
All-cause mortality
Incidence of transplant related mortality (TRM) within 100 days and within 1 year post-CTX001 infusion
Incidence of transplant related mortality (TRM) within 100 days and within 1 year post-CTX001 infusion
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
Proportion of subjects achieving TI12, defined as maintaining weighted average Hb ≥9 g /dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion. The evaluation of TI12 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.
Proportion of subjects achieving TI12, defined as maintaining weighted average Hb ≥9 g /dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion. The evaluation of TI12 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.
次要结局
- Proportion of subjects achieving TI6, defined as maintaining weighted average Hb ≥9 g /dL without RBC transfusions for at least 6 consecutive months any time after CTX001 infusion. The evaluation of TI6 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.
- Proportion of subjects achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions up to 24 months starting 60 days after CTX001 infusion.
- Relative change from baseline in transfusions up to 24 months starting 60 days after CTX001 infusion
- Duration of transfusion free in subjects who have achieved TI12
- Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time. Intended genetic modifications are indels that modify the sequence of the erythrocyte-specific enhancer in intron 2 of BCL11A
- Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time
- Fetal hemoglobin concentration (pre-transfusion) over time
- Total hemoglobin concentration (pre-transfusion) over time
- Change in patient reported outcomes (PROs) over time using EuroQol Quality of Life Scale (EQ-5D-5L for subjects ≥18 years old, EQ-5D-Y for subjects <18 years old), functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) for subjects ≥18 years old, and Pediatric Quality of Life Inventory (PedsQL) for subjects <18 years old.
- Change in parameters of iron overload, including: o Liver iron concentration (LIC ) from baseline as assessed by R2 magnetic resonance imaging (MRI ) and cardiac iron content (CIC ) from baseline as assessed by T2 * MRI o Change in serum ferritin level from baseline over time
- Proportion of subjects receiving iron chelation therapy over time