A Study Evaluating the Safety and Efficacy of the LentiGlobin® BB305 Drug Product in Beta-Thalassemia Major Subjects

Inclusion criteria:

• Subjects between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
• Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years.
• Eligible for allogeneic bone marrow transplant.
• Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion criteria:

• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
• A white blood cell (WBC) count <3 × 109/L, and / or platelet count <100 × 109/L if not due to hypersplenism.
• Uncorrected bleeding disorder.
• Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis).
• Receipt of an allogeneic transplant.
• Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
• Kidney disease with a calculated creatinine clearance <30% normal value.
• Uncontrolled seizure disorder.
• Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin).
• 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.
• Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
• Participation in another clinical study with an investigational drug within 30 days of Screening.
• Any prior or current malignancy or myeloproliferative disorder.
• Prior receipt of gene therapy.