A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia
Condition: Beta-Thalassemia
MeSH terms: Thalassemia; beta-Thalassemia
Intervention: LentiGlobin BB305 Drug Product
Intervention description: LentiGlobin BB305 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 0 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.