A Phase I/II Study of Nula-cel in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 7
- 主要终点
- Proportion of patients who reach neutrophil engraftment
研究概览
简要总结
This study is a first-in-human, single-arm, open-label Phase I/II study of nula-cel in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.
详细描述
Participants diagnosed with severe SCD will receive nula-cel via IV infusion following myeloablative conditioning in an autologous HSCT setting.
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
- 12 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥12 to ≤ 40 years
- •Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
- •recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
- •ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
- •Lansky/Karnofsky performance status of ≥ 80
排除标准
- •Available 10/10 HLA-matched sibling donor
- •Prior HSCT or gene therapy
- •Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
- •Clinically significant and active bacterial, viral, fungal or parasitic infection
- •Pregnancy or breastfeeding in a postpartum female
- •Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment
研究组 & 干预措施
nula-cel Drug Product
nula-cel Drug Product is a human autologous CRISPR-Cas9 edited and sickle mutation-corrected HSPC product.
干预措施: nula-cel Drug Product (Genetic)
结局指标
主要结局
Proportion of patients who reach neutrophil engraftment
时间窗: 42 days post-infusion
Incidence rate of treatment-related mortality
时间窗: 12 months post-infusion
Overall survival
时间窗: 24 months post-infusion
Frequency and severity of AEs/SAEs
时间窗: 24 months post-infusion
Incidence rate of treatment-related mortality
时间窗: 100 days post-infusion
次要结局
- Change in annualized packed red blood cell (pRBC) transfusion requirements (volume and frequency) for SCD indications(through study completion, up to 24 months post-infusion)
- Proportion of participants with complete resolution of severe vaso-occlusive crises (sVOCs)(over time, from 6 months to 18 months post-infusion)
- Time to neutrophil engraftment(through study completion, up to 24 months post-infusion)
- Time to platelet engraftment(through study completion, up to 24 months post-infusion)
- Evaluation of gene correction levels in peripheral myeloid cells(through study completion, up to 24 months post-infusion)
- Evaluation of adult Hgb as a percentage of total Hgb(through study completion, up to 24 months post-infusion)
- Evaluation of HbS as a percentage of total Hgb(through study completion, up to 24 months post-infusion)
- Total Hgb without disease-indicated transfusion support(through study completion, up to 24 months post-infusion)
- Incidence rate of any sVOCs(over time, from 6 months to study completion, up to 24 months post-infusion)
- Proportion of participants achieving HbS <50% for at least 3 months(through study completion, up to 24 months post-infusion)
- Evaluation of globin chain expression compared to baseline(through study completion, up to 24 months post-infusion)