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

Vertex Pharmaceuticals Incorporated6 个研究点分布在 4 个国家目标入组 26 人2022年8月2日

干预措施CTX001

概览

阶段: 3 期
干预措施: CTX001
疾病 / 适应症: 未指定
发起方: Vertex Pharmaceuticals Incorporated
入组人数: 26
试验地点: 6
主要终点: Fetal Hemoglobin (HbF) Concentration Over Time
状态: 招募中
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

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.

注册库

clinicaltrials.gov

开始日期

2022年8月2日

结束日期

2027年6月9日

最后更新

上个月

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Vertex Pharmaceuticals Incorporated

责任方

Sponsor

入排标准

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

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

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)