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

Bluebird Bio

Status and phase: Completed; Phase 3

Conditions: Beta-Thalassemia

Treatments: Genetic: LentiGlobin BB305 Drug Product

Study type: Interventional

Funder types: Industry

Identifiers

NCT03207009

HGB-212

Details and patient eligibility

About

This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (<=) 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.

Enrollment: 19 patients

Sex: All

Ages: Under 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants less than or equal to (<=) 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.

Exclusion criteria

• Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least one β-globin gene (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 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.
• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

LentiGlobin BB305 Drug Product

Experimental group

Description:

LentiGlobin BB305 Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human βA-T87Q-globin)

Treatment:

Genetic: LentiGlobin BB305 Drug Product