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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. Identifier: NCT03207009
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : June 24, 2021
Information provided by (Responsible Party):
bluebird bio

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.

Condition or disease Intervention/treatment Phase
Beta-Thalassemia Genetic: LentiGlobin BB305 Drug Product Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 8, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Arm Intervention/treatment
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)
Genetic: LentiGlobin BB305 Drug Product
LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Other Name: betibeglogene autotemcel

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. Engraftment defined as an absolute neutrophil count ≥500 cells/µL for 3 consecutive days [ Time Frame: 24 months post-transplant ]
  4. Detection of vector-derived replication competent lentivirus (RCL) using a RCL screening assay [ Time Frame: 24 months post-transplant ]
  5. The number of subjects with insertional oncogenesis (myelodysplasia, leukemia, lymphoma, etc.). [ Time Frame: 24 months post-transplant ]
  6. Frequency of clinical adverse events [ Time Frame: 24 months post-transplant ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03207009

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United States, California
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Hopital d'enfants de la Timone
Marseille, France, 13385
Hannover Medical School
Hannover, Germany, 30625
University of Heidelberg
Heidelberg, Germany, 69120
General Hospital of Thessaloniki 'G.Papanikolaou'
Thessaloníki, Greece
IRCCS Ospedale Pediatrico Babino Gesu
Rome, Italy
United Kingdom
University College London Hospital
London, United Kingdom
Sponsors and Collaborators
bluebird bio
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Study Director: Richard Colvin bluebird bio
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Responsible Party: bluebird bio Identifier: NCT03207009    
Other Study ID Numbers: HGB-212
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: June 24, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn