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A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects With Transfusion-Dependent β-Thalassemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03207009
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
bluebird bio

Tracking Information
First Submitted Date  ICMJE June 29, 2017
First Posted Date  ICMJE July 2, 2017
Last Update Posted Date February 16, 2021
Actual Study Start Date  ICMJE June 8, 2017
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2021)
The proportion of treated subjects who meet the definition of "transfusion independence" (TI). TI is defined as Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion. [ Time Frame: 12-24 months post-transplant ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
The proportion of subjects who meet the definition of "transfusion reduction" (TR). [ Time Frame: 24 months post-transplant ]
TR is defined as demonstration of reduction in volume of RBC transfusion requirements (in mL/kg) in the post-treatment time period of Months 12 to 24 compared to the average annual transfusion requirement in the 24 months prior to enrollment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2021)
  • The proportion of subjects who meet the definition of "transfusion reduction" (TR). [ Time Frame: 12-24 months post-transplant ]
    TR is defined as demonstration of reduction in volume of RBC transfusion requirements (in mL/kg) in the post-treatment time period of Months 12 to 24 compared to the average annual transfusion requirement in the 24 months prior to enrollment.
  • Percentage of subjects with a reduction in the mL/kg RBC transfused from Month 12 through Month 24 after drug product infusion of at least 50% compared to the average annual RBC transfusion requirement during the 2 years prior to enrollment. [ Time Frame: 12-24 months post-transplant ]
  • Engraftment defined as an absolute neutrophil count ≥500 cells/µL for 3 consecutive days [ Time Frame: 24 months post-transplant ]
  • Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay [ Time Frame: 24 months post-transplant ]
  • The number of subjects with insertional oncogenesis (myelodysplasia, leukemia, lymphoma, etc.). [ Time Frame: 24 months post-transplant ]
  • Frequency of clinical adverse events [ Time Frame: 24 months post-transplant ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
  • The proportion of treated subjects who meet the definition of "transfusion independence" (TI). TI is defined as Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion. [ Time Frame: 12-24 months post-transplant ]
  • Percentage of subjects with a reduction in the mL/kg RBC transfused from Month 12 through Month 24 after drug product infusion of at least 50% compared to the average annual RBC transfusion requirement during the 2 years prior to enrollment. [ Time Frame: 24 months post-transplant ]
  • Frequency of events of insertional mutagenesis leading to clonal dominance or leukemia. [ Time Frame: 24 months post-transplant ]
  • Frequency of clinical adverse events [ Time Frame: 24 months post-transplant ]
  • Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay [ Time Frame: 24 months post-transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects With Transfusion-Dependent β-Thalassemia
Official Title  ICMJE A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age
Brief Summary This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 subjects ≤50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Beta-Thalassemia
Intervention  ICMJE Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Name: betibeglogene autotemcel
Study Arms  ICMJE Experimental: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human βA-T87Q-globin)
Intervention: Genetic: LentiGlobin BB305 Drug Product
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 22, 2019)
18
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2017)
15
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects ≤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 DMC has approved enrolling subjects younger than 5 years of age, subjects younger than 5 years of age may be enrolled if they weigh a minimum of 6 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 mL/kg/year of packed red blood cells (pRBCs) in the 2 years preceding enrollment (all subjects), or be managed under standard thalassemia guidelines with ≥8 transfusions of pRBCs per year in the 2 years preceding enrollment (subjects ≥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.

Exclusion Criteria:

  • Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least one HBB allele.
  • 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 <3×10^9/L, and/or platelet count <100×10^9/L not related to hypersplenism.
  • Uncorrected bleeding disorder.
  • Any prior or current malignancy.
  • Prior HSCT.
  • Advanced liver disease.
  • A cardiac T2* <10 ms by magnetic resonance imaging (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 subject 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 subjects.
  • A known and available HLA-matched family donor.
  • Any contraindications to the use of 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Greece,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03207009
Other Study ID Numbers  ICMJE HGB-212
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party bluebird bio
Study Sponsor  ICMJE bluebird bio
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Richard Colvin bluebird bio
PRS Account bluebird bio
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP