NCT02906202已完成3 期
A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype, by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- Percentage of Participants Who Meet the Definition of Transfusion Independence (TI)
研究概览
简要总结
This is a single-arm, multi-site, single-dose, Phase 3 study in 23 participants less than or equal to (<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), also known as β-thalassemia major, who do not have a β0 mutation at both alleles of the hemoglobin β (HBB) gene. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
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
- 0 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants <= 50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Provided that the Data Monitoring Committee (DMC) has approved enrolling participants younger than 5 years of age, participants younger than 5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.
- •Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year (mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be managed under standard thalassemia guidelines with >= 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants >= 12 years).
- •Clinically stable and eligible to undergo (HSCT).
- •Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
排除标准
- •Presence of a mutation characterized as β0 mutation at both alleles of the β-globin gene HBB.
- •Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
- •A white blood cell (WBC) count less than (<) 3×10^9/Liter (L), and/or platelet count < 100×10^9/L not related to hypersplenism.
- •Uncorrected bleeding disorder.
- •Any prior or current malignancy.
- •Immediate family member with a known Familial Cancer Syndrome.
- •Prior HSCT.
- •Advanced liver disease.
- •A cardiac T2* < 10 ms by MRI.
- •Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
- •Participation in another clinical study with an investigational drug within 30 days of Screening.
- •Any other condition that would render the participant ineligible for HSCT, as determined by the attending transplant physician or investigator.
- •Prior receipt of gene therapy.
- •Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participant.
- •A known and available Human leukocyte antigen (HLA) matched family donor.
- •Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
结局指标
主要结局
Percentage of Participants Who Meet the Definition of Transfusion Independence (TI)
时间窗: From 14 to 24 months post-transplant
TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion.
次要结局
- Duration of Transfusion Independence (TI)(From start of TI up to Month 24)
- Annualized Volume of pRBC Transfusions(From 12 months post-drug product infusion through Month 24)
- Weighted Average Nadir Hemoglobin (Hb)(12 months post-drug product infusion through Month 24)
- Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24(At Month 6, 9, 12, 18 and 24)
- Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score(Baseline, Months 12 and 24)
- Annualized Number of pRBC Transfusions(From 12 months post-drug product infusion through Month 24)
- Time From Drug Product Infusion to Last pRBC Transfusion(From start of drug product infusion up to Month 24)
- Time From Last Iron Chelation Use to Last Follow-up(Time from last iron chelation up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window))
- Change From Baseline in Liver Iron Concentration by Magnetic Resonance Imaging (MRI)(Baseline, Months 12 and 24)
- Percentage of Participants Who Meet the Definition of Transfusion Independence (TI) at Month 24(At Month 24 post-transplant)
- Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)(From 14 months post-drug product infusion through Month 24)
- Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume(12 months post-drug product infusion through Month 24)
- Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24(At Month 6, 9, 12, 18 and 24)
- Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI)(From 60 days after the last pRBC transfusion through Month 24)
- Time From Last pRBC Transfusion to Month 24(From last pRBC Transfusion up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window))
- Percentage of Participants Who Used Therapeutic Phlebotomy Post Drug Product (DP) Infusion(Up to Month 24)
- Annualized Phlebotomy Therapy Usage Following Drug Product Infusion(Up to Month 24)
- Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion(Up to Month 24)
- Change From Baseline in Cardiac T2* on MRI(Baseline, Months 12 and 24)
- Change From Baseline in Serum Ferritin at Months 12 and 24(Baseline, Months 12 and 24)
- Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24(Baseline, Months 12 and 24)
- Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24(Baseline, Months 12 and 24)
- Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24(Baseline, Months 12 and 24)
- Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24(Baseline, Months 12 and 24)
研究者
研究点 (8)
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