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A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype

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: NCT02906202
Recruitment Status : Active, not recruiting
First Posted : September 20, 2016
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
bluebird bio

Tracking Information
First Submitted Date  ICMJE August 19, 2016
First Posted Date  ICMJE September 20, 2016
Last Update Posted Date December 24, 2020
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2017)
The proportion of treated subjects who meet the definition of "transfusion independence" (TI). [ Time Frame: 12 - 24 months post-transplant ]
TI is defined as a weighted average Hb ≥9g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after drug product infusion.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2016)
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
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, Who do Not Have a β0/β0 Genotype
Official Title  ICMJE 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
Brief Summary This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 23 subjects ≤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.
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+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene)
Intervention: Genetic: LentiGlobin BB305 Drug Product
Publications * Hamed EM, Meabed MH, Aly UF, Hussein RRS. Recent Progress in Gene Therapy and Other Targeted Therapeutic Approaches for Beta Thalassemia. Curr Drug Targets. 2019;20(16):1603-1623. doi: 10.2174/1389450120666190726155733. Review.

*   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
Estimated Enrollment  ICMJE
 (submitted: February 6, 2018)
23
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2016)
15
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 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 hematopoietic stem cell therapy (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 β0 mutation at both alleles of the HBB gene.
  • 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.
  • Immediate family member with a known Familial Cancer Syndrome.
  • 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,   Italy,   Thailand,   United Kingdom,   United States
Removed Location Countries Greece
 
Administrative Information
NCT Number  ICMJE NCT02906202
Other Study ID Numbers  ICMJE HGB-207
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
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 December 2020

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