This is a non-randomized, open label, multi-site, single dose, Phase 3 study in approximately 35 adults and pediatric subjects > 2 and < 50 years of ages with SCD. The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using LentiGlobin BB305 Drug Product, an autologous CD34+ cell-enriched population that contains hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector (LVV) encoding beta A-T87Q-globin gene, suspended in cryopreservation solution in the final immediate container for the intended medical use.
- Have a diagnosis of SCD, with either betaS/betaS, beta S/beta-0 or beta S/beta + genotype
- Be > 2 and <50 years of age at time of consent.
- Weigh a minimum of 6 kg and reasonably be anticipated to be able to provide at least the minimum number of cells require to initiate the manufacturing process.
- Applicable to subjects <18 years of age only: availability of a willing, matched human leukocyte antigen (HLA)-identical sibling hematopoietic cell donor
- Severe cerebral vasculopathy, defined by any history of: overt ischemic or hemorrhagic stroke, abnormal transcranial Doppler (>200 cm/sec based on central read) requiring chronic transfusion, occlusion, or stenosis in the circle of Willis, or presence of Moyamoya disease (central read of brain imaging MRI [or computed tomography (CT) scan if MRI not feasible to perform]). Subjects with radiologic evidence of silent infarction in the absence of any of the above criteria would still be eligible.
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1) or -2 (HTLV-2), active syphilis. Not that subjects who have been vaccinated against hepatitis B [hepatitis B surface B antibody-positive] are eligible. Subjects with past exposure to HBV [HBc Ab positive and/or HBe Ab positive] are also eligible for the study provided they are negative for HBV DNA. Subjects who are positive for anti-hepatitis C antibody are eligible as long as they have an undetectable hepatitis C viral load. Where clinically and/or regionally indicated, other tests may be performed, in which case relevant positive results suggesting active infection would exclude the subject from participating, depending on regional guidelines: for example, malaria, tuberculosis, active toxoplasmosis, Trypanosoma cruzi, or West Nile Virus.
Time between Screening and drug product infusion will be variable and is estimated generally to be between 3 to 5 month (e.g., up to 3 months between Screening and Mobilization, followed by approximately 2 months before drug product infusion). Thereafter the subject is planned to remain on study for approximately 24 months. Eligible subject will then be asked to enroll in a separate long-term follow-up study until approximately 15 years post drug product infusion.