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临床试验/NCT04208529
NCT04208529Enrolling By Invitation3 期

A Long-term Follow-up Study of Subjects With β-thalassemia or Sickle Cell Disease Treated With Autologous CRISPR-Cas9 Modified Hematopoietic Stem Cells (CTX001)

Vertex Pharmaceuticals Incorporated24 个研究点 分布在 6 个国家目标入组 160 人开始时间: 2021年1月20日最近更新:
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适应症
干预措施

试验速览

阶段
3 期
状态
Enrolling By Invitation
入组人数
160
试验地点
24
主要终点
Serious adverse events (SAEs)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multi-site, open- label rollover study to evaluate the long-term safety and efficacy of CTX001 in pediatric and adult participants who received CTX001 in parent studies 111 (NCT03655678) 141 (NCT05356195) or 161 (NCT05477563) (transfusion-dependent β-thalassemia [TDT] studies) or Study 121 (NCT03745287) or 151 (NCT05329649) or 161(NCT05477563) (severe sickle cell disease [SCD] studies).

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Other
盲法
None

入排标准

年龄范围
2 Years 至 —（Child, Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participants (or his or her legally appointed and authorized representative or guardian) must sign and date informed consent form (ICF) and, where applicable, an assent form
  • •Participants must have received CTX001 infusion in a parent study

排除标准

  • •There are no exclusion criteria

研究组 & 干预措施

CTX001

Experimental

All participants who complete or discontinue one of the multiple parent studies (CTX001-111, CTX001-121, CTX001-141, CTX001-151 and CTX001-161) after CTX001 infusion will be asked to participate in this long-term follow-up study.

干预措施: CTX001 (Biological)

结局指标

主要结局

Serious adverse events (SAEs)

时间窗: Signing of informed consent up to 15 years post CTX001 infusion

New or worsening hematologic disorders

时间窗: Signing of informed consent up to 15 years post CTX001 infusion

All-cause mortality

时间窗: Signing of informed consent up to 15 years post CTX001 infusion

CTX001-related adverse events (AEs)

时间窗: Signing of informed consent up to 15 years post CTX001 infusion

New malignancies

时间窗: Signing of informed consent up to 15 years post CTX001 infusion

次要结局

  • SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS)(Up to 5 years post CTX001 infusion)
  • TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized volume of RBC transfusions starting after month 10 after CTX001 infusion for participants who have not achieved TI12(From Month 10 up to 15 years post-CTX001 infusion)
  • TDT: Relative reduction from baseline in annualized volume of RBC transfusions starting after Month 10 after CTX001 infusion for participants who have not achieved TI12(From Month 10 up to 15 years post-CTX001 infusion)
  • TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants(Up to 8 years post CTX001 infusion for LIC; up to 5 years post CTX001 infusion for CIC and up to 15 years post CTX001 infusion for ferritin)
  • TDT: Proportion of participants receiving iron removal therapy over time(Up to 15 years post CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 3 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 6 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 12 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Change in volume of RBCs transfused for SCD-related indications over time(Up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in reticulocytes/erythrocytes over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in lactate dehydrogenase (LDH) over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in haptoglobin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in total bilirubin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in indirect bilirubin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS)(Up to 5 years post CTX001 infusion)
  • SCD: Change in PROs over time assessed using Wong Baker FACES pain scale(Up to 5 years post CTX001 infusion)
  • SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Fetal Hemoglobin (HbF) concentration over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Total Hemoglobin (Hb) concentration over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time(Up to 15 years post CTX001 infusion)
  • TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT: Duration of transfusion free in participants who have achieved TI12(From 60 days after last RBC transfusion up to 15 years post CTX001 infusion)
  • SCD: Proportion of participants who have not experienced any severe vaso-occlusive crises (VOC) for at least 12 consecutive months (VF12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with SCD free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with at least 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Relative change from baseline in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Duration of severe VOC free in participants who have achieved VF12(From 60 days after last RBC transfusion up to 15 years post CTX001 infusion)
  • SCD: Relative change from baseline in rate of inpatient hospitalizations for severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Relative change from baseline in annualized duration of hospitalization for severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111 and 121 only(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for participants from study 111, 121 and 161 only(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants <18 years assessed using EQ-5D-Youth (EQ-5D-Y) from study 111,121,141 and 151 only(Up to 5 years post CTX001 infusion)
  • SCD: Change in SCD-specific PROs over time in participants ≥18 years of age assessed using adult sickle cell quality of life measurement system (ASCQ-Me) (participants from Study 121 and 161 only)(Up to 5 years post CTX001 infusion)
  • SCD: Change in SCD-specific PROs over time in participants <18 years of age assessed using PedsQL Generic Core SCD module from studies 111,121,141,151 and 161(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Total Hemoglobin (Hb) concentration over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Fetal Hemoglobin (HbF) concentration over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time(Up to 15 years post CTX001 infusion)
  • TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111,121 and 171 only(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for participants from study 111, 121, 161 and 171 only(Up to 5 years post CTX001 infusion)
  • SCD: Proportion of participants with at least 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants <18 years assessed using EQ-5D-Youth (EQ-5D-Y) from study 111,121,141,151 and 171 only(Up to 5 years post CTX001 infusion)
  • TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core(Up to 5 years post CTX001 infusion)
  • TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized volume of RBC transfusions starting after month 10 after CTX001 infusion for participants who have not achieved TI12(From Month 10 up to 15 years post-CTX001 infusion)
  • TDT: Duration of transfusion free in participants who have achieved TI12(From 60 days after last RBC transfusion up to 15 years post CTX001 infusion)
  • TDT: Relative reduction from baseline in annualized volume of RBC transfusions starting after Month 10 after CTX001 infusion for participants who have not achieved TI12(From Month 10 up to 15 years post-CTX001 infusion)
  • TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants(Up to 8 years post CTX001 infusion for LIC; up to 5 years post CTX001 infusion for CIC and up to 15 years post CTX001 infusion for ferritin)
  • TDT: Proportion of participants receiving iron removal therapy over time(Up to 15 years post CTX001 infusion)
  • SCD: Proportion of participants who have not experienced any severe vaso-occlusive crises (VOC) for at least 12 consecutive months (VF12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with SCD free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Relative change from baseline in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Duration of severe VOC free in participants who have achieved VF12(From 60 days after last RBC transfusion up to 15 years post CTX001 infusion)
  • SCD: Relative change from baseline in rate of inpatient hospitalizations for severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Relative change from baseline in annualized duration of hospitalization for severe VOCs(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 3 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 6 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Proportion of participants with sustained HbF ≥20% for at least 12 months(From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion)
  • SCD: Change in volume of RBCs transfused for SCD-related indications over time(Up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in reticulocytes/erythrocytes over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in lactate dehydrogenase (LDH) over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in haptoglobin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in total bilirubin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change from baseline in indirect bilirubin over time(From baseline up to 15 years post CTX001 infusion)
  • SCD: Change in SCD-specific PROs over time in participants ≥18 years of age assessed using adult sickle cell quality of life measurement system (ASCQ-Me) (participants from Study 121,161 and 171 only)(Up to 5 years post CTX001 infusion)
  • SCD: Change in SCD-specific PROs over time in participants <18 years of age assessed using PedsQL Generic Core SCD module from studies 111,121,141,151,161 and 171(Up to 5 years post CTX001 infusion)
  • SCD: Change in PROs over time assessed using Wong Baker FACES pain scale(Up to 5 years post CTX001 infusion)
  • SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale(Up to 5 years post CTX001 infusion)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (24)

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