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临床试验/NCT04293185
NCT04293185进行中（未招募）3 期

A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the BB305 Lentiviral Vector in Subjects With Sickle Cell Disease

Genetix Biotherapeutics Inc.18 个研究点 分布在 1 个国家目标入组 35 人开始时间: 2020年2月14日最近更新:
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适应症

试验速览

阶段
3 期
状态
进行中（未招募）
入组人数
35
试验地点
18
主要终点
VOE-CR
研究概览研究设计入排标准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 non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using bb1111 (also known as LentiGlobin BB305 Drug Product for SCD).

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
2 Years 至 50 Years（Child, Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
  • •Be ≥2 and ≤50 years of age at time of consent.
  • •Weigh a minimum of 6 kg.
  • •Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
  • •Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
  • •In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
  • •Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
  • •Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
  • •Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).

排除标准

  • •Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
  • •Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
  • •Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
  • •Clinically significant, active bacterial, viral, fungal, or parasitic infection
  • •Advanced liver disease, such as
  • •clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
  • •liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
  • •Inadequate bone marrow function, as defined by an absolute neutrophil count of <1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L.
  • •Any contraindications to the use of 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.
  • •Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
  • •Unable to receive pRBC transfusion.
  • •Prior receipt of an allogeneic transplant.
  • •Prior receipt of gene therapy.
  • •Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
  • •Immediate family member with a known or suspected Familial Cancer Syndrome.
  • •Female subject is breastfeeding, pregnant or will attempt to become pregnant from Screening to at least 6 months after drug product infusion.
  • •Any other condition that would render the subject ineligible for HSCT.
  • •Participation in another clinical study with an investigational drug within 30 days of screening.
  • •Presence of a chromosomal abnormality or genetic mutation that may put the subject at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) per Investigator's judgment.
  • •Presence of genetic mutations that result in the inactivation of 2 or more α-globin genes

结局指标

主要结局

VOE-CR

时间窗: 6-18 months post-transplant

Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion

次要结局

  • sVOE-CR(6-18 months post-transplant)
  • Weighted average HbS percentage of non-transfused total Hb(Month 6, 12, 18 and 24 post-transplant)
  • Weighted average non-HbS percentage of non-transfused total Hb(Month 6, 12, 18 and 24 post-transplant)
  • Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent(1-24 months post-transplant)
  • Weighted average HbS percentage of non-transfused total Hb ≤70%, ≤60%, ≤50%(Month 6, 12, 18 and 24 post-transplant)
  • Average and median of HbS percentage of non-transfused total Hb(1-24 months post-transplant)
  • Average and median of non-HbS percentage of non-transfused total Hb(1-24 months post-transplant)
  • Change from baseline in absolute reticulocyte count(1-24 months post-transplant)
  • Change from baseline in total bilirubin(1-24 months post-transplant)
  • Change from baseline in lactate dehydrogenase(1-24 months post-transplant)
  • Change from baseline in liver iron content(1-24 months post-transplant)
  • sVOE-CR24(6-24 months post-transplant)
  • Change from baseline in annualized volume of pRBC transfusions(6-24 months post-transplant)
  • Change from baseline in annualized number of SCD-related hospital admissions(1 - 24 months post-transplant)
  • Proportion of subjects achieving Globin Response(6-24 months post-transplant)
  • VOE-CR24(6-24 months post-transplant)
  • sVOE-75(1-24 months post-transplant)
  • Weighted average non-transfused total Hb(Month 6, 12, 18 and 24 post-transplant)
  • Weighted average HbAT87Q percentage of non-transfused total Hb(Month 6, 12, 18 and 24 post-transplant)
  • Average and median of non-transfused total Hb(1-24 months post-transplant)
  • Change from baseline in haptoglobin(1-24 months post-transplant)
  • Change from baseline in erythropoietin(1-24 months post-transplant)
  • Change in the annualized number of severe VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent.(1-24 months post-transplant)
  • Change from baseline in ferritin(1-24 months post-transplant)
  • Change from baseline in patient-reported quality of life, as measured by PROMIS-57 Version 2.1 for subjects ≥ 18 years of age and PROMIS Pediatric Profile/Parent Proxy Profile 49 Version 2.0 for subjects < 18 years of age(1 - 24 months post-transplant)
  • Average and median of HbAT87Q percentage of non-transfused total Hb(1-24 months post-transplant)
  • Change from baseline in percent reticulocytes(1-24 months post-transplant)
  • Change from baseline in percent erythrocytes(1-24 months post-transplant)
  • Change from baseline in cardiac iron content (if assessed at baseline)(1-24 months post-transplant)
  • Change from baseline in serum transferrin receptor(1 - 24 months post-transplant)
  • Change from baseline in annualized frequency of packed red blood cell (pRBC) transfusions(6-24 months post-transplant)
  • Change from baseline in TCD velocity at Month 12 and Month 24 (for subjects ≤ 16 years old at Informed Consent)(Month 12 and Month 24 post-transplant)
  • Change from baseline in meters walked during the 6-minute walk test(1 - 24 months post-transplant)
  • Change from baseline in annualized number of total days hospitalized(1 - 24 months post-transplant)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (18)

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