A Phase 1/2, Open-Label, Multicenter, Single-Arm Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 5
- 主要终点
- Percentage of Participants With Successful Engraftment
研究概览
简要总结
This is an open label, multicenter, Phase 1/2 study in approximately eight adults with severe Sickle Cell Disease (SCD). The study will evaluate the safety, tolerability, and efficacy of autologous hematopoietic stem cell transplantation using BIVV003.
详细描述
Subject participation in this study will be approximately 136 weeks. Enrolled subjects will be asked to participate in a separate long-term follow-up study to monitor the safety and efficacy of BIVV003 treatment for a total of 15 years post-transplant.
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
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation
- •Previous treatment with gene therapy
- •Current enrollment in an interventional study or having received an investigational drug within 30 days of study enrollment
- •Pregnant or breastfeeding female
- •Female or male who plans to become pregnant or impregnate a partner, respectively, during the anticipated study period
- •Contraindication to plerixafor, apheresis, or busulfan
- •Treatment with prohibited medication in previous 30 days
- •Known allergy or hypersensitivity to plerixafor, busulfan, or investigational product excipients
- •History of active malignancy within past 5 years, any history of hematologic malignancy, or a family history of a cancer predisposition syndrome (without negative result of candidate)
- •Current diagnosis of uncontrolled seizures
- •History of significant bleeding disorder
- •Clinically significant infection
- •Any major organ dysfunction involving brain, kidney, liver, lung, or heart (e.g., congestive heart failure, pulmonary hypertension)
- •Corrected QT interval of more than 500 millisecond (ms) based on screening electrocardiogram (ECG)
- •Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- •Known to have a gamma-globin variant associated with altered oxygen affinity
- •Hereditary persistence of fetal hemoglobin (HPFH) or HbF concentration of more than or equal to 20 percent (%) at screening
- •Absolute Neutrophil Count (ANC) of less than or equal to 1,000 per microliter
- •Platelet count of less than 100,000 per microliter
- •History of platelet alloimmunization (precluding ability to provide transfusion support)
- •Extensive Red Blood Cell (RBC) alloimmunization (precluding ability to provide transfusion support)
- •Judged unsuitable for participation by investigator and/or sponsor
研究组 & 干预措施
BIVV003
Participants will receive plerixafor as subcutaneous (SQ) administration followed by myeloablative conditioning therapy with intravenous (IV) busulfan. BIVV003 will then be administered as a 1-time IV infusion of autologous Cluster of Differentiation 34 + Hematopoietic Stem/Progenitor Cell (CD34+HSPC) transfected ex vivo with zinc finger nuclease (ZFN) messenger ribonucleic acid (mRNAs) targeting the B-cell lymphoma/leukemia 11A (BCL11A) locus.
干预措施: Plerixafor (Biological)
BIVV003
Participants will receive plerixafor as subcutaneous (SQ) administration followed by myeloablative conditioning therapy with intravenous (IV) busulfan. BIVV003 will then be administered as a 1-time IV infusion of autologous Cluster of Differentiation 34 + Hematopoietic Stem/Progenitor Cell (CD34+HSPC) transfected ex vivo with zinc finger nuclease (ZFN) messenger ribonucleic acid (mRNAs) targeting the B-cell lymphoma/leukemia 11A (BCL11A) locus.
干预措施: Busulfan (Drug)
BIVV003
Participants will receive plerixafor as subcutaneous (SQ) administration followed by myeloablative conditioning therapy with intravenous (IV) busulfan. BIVV003 will then be administered as a 1-time IV infusion of autologous Cluster of Differentiation 34 + Hematopoietic Stem/Progenitor Cell (CD34+HSPC) transfected ex vivo with zinc finger nuclease (ZFN) messenger ribonucleic acid (mRNAs) targeting the B-cell lymphoma/leukemia 11A (BCL11A) locus.
干预措施: BIVV003 (Genetic)
结局指标
主要结局
Percentage of Participants With Successful Engraftment
时间窗: Up to Day 42
Successful engraftment is defined by absolute neutrophil count (ANC) greater than or equal to \>=500 cells/microliter (mL) for 3 consecutive days.
Number of Participants With Adverse Events (AEs)
时间窗: Up to Week 104
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to Week 104
An SAE is any untoward medical occurrence that at any dose: Results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); however, this does not include an event that, had it occurred in a more severe form, might have caused death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Percentage of Participants who are Alive at Post-transplantation Day 100
时间窗: Day 100
The percentage of participants who are alive at post-transplantation Day 100 will be calculated using the Kaplan-Meier estimate.
Percentage of Participants who are Alive at Post-transplantation Week 52
时间窗: Week 52
The percentage of participants who are alive at post-transplantation Week 52 will be calculated using the Kaplan-Meier estimate.
Percentage of Participants who are Alive at Post-transplantation Week 104
时间窗: Week 104
The percentage of participants who are alive at post-transplantation Week 104 will be calculated using the Kaplan-Meier estimate.
次要结局
- CD34 + HSPC Yield from Plerixafor Stem Cell Mobilization(Approximately 12 weeks)
- Proportion of Participants with Sufficient Stem Cell Mobilization for Rescue Aliquot and BIVV003 Production(Approximately 12 weeks)
- Yield of Zinc Finger Nuclease (ZFN)-edited Investigational Product(Approximately 12 weeks)
- Time to Initial Neutrophil Recovery Following BIVV003 Infusion(Up to Week 104)
- Percentage of Participants With Maintenance of Platelet count of >=50,000/mcL to last Participant Visit(Up to Week 104)
- Change From Baseline in Peripheral Blood Fetal Hemoglobin (HbF) Levels(Baseline up to Week 104)
- Change From Baseline in Peripheral Blood Percent (%)F cells(Baseline up to Week 104)
- Change From Baseline in Peripheral Blood Sickle Hemoglobin (HbS) Levels(Baseline up to Week 104)
- Change From Baseline in Peripheral blood total hemoglobin (Hb) concentration(Baseline up to Week 104)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System 57 (PROMIS-57) Scale Score(Baseline up to Week 104)
- Number of Participants With Sickle Cell Disease (SCD)-related Clinical Events(Baseline up to Week 104)
- Number of Red Blood Cell (RBC) Transfusions Received During the Post-transplantation Study Period(Up to Week 104)
- Time to Platelet Recovery Following BIVV003 Infusion(Up to Week 104)
- Percentage of Participants With Maintenance of Absolute Neutrophil Count (ANC) of >=500/mcL to last Participant Visit(Up to Week 104)
- Change From Baseline in Serum Bilirubin Levels(Baseline up to Week 104)
- Change From Baseline in Reticulocyte Count(Baseline up to Week 104)
- Change From Baseline in Lactate Dehydrogenase (LDH) Levels(Baseline up to Week 104)
- Change From Baseline in Haptoglobin Levels(Baseline up to Week 104)
- Number of SCD Related Clinical Events by Severity(Baseline up to Week 104)
- Participants lymphocyte Counts(At Weeks 13 and 52)
- Participants Immunoglobulin levels(At Weeks 13 and 52)
- Total Volume of RBC Transfused(Up to Week 104)