4 United States sites
2 to 50 Years
– Have a diagnosis of SCD, with either βS/βS, βS/β0 or βS/β+ genotype.
– Be ≥2 and ≤50 years of age at time of consent.
– Weigh a minimum of 6 kg.
– Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance
status of ≥60 (<16 years of age). - Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history. - Have severe manifestations of SCD. i.e. in the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 severe VOEs in the 24 months prior to informed consent as defined below. For the purposes of this study, a severe VOE is defined as an event with no medically determined cause other than a vaso-occlusion, requiring a ≥24 -hour hospital or emergency room (ER) observation unit visit or at least 2 visits to a day unit or ER over 72 hours with both visits requiring intravenous treatment. Exception: priapism does not require hospital admission but does require a medical facility visit; 4 priapism episodes that require a visit to a medical facility (without inpatient admission) are sufficient to meet criterion. - Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
– Applicable to subjects <18 years of age only: Availability of a willing, matched human
leukocyte antigen (HLA)-identical sibling HSC 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
– Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2),
hepatitis B, hepatitis C, human T-lymphotrophic virus-1 (HTLV-1) or -2 (HTLV-2),
– Clinically significant, active bacterial, viral, fungal, or parasitic infection
– Advanced liver disease, such as
1. clear evidence of liver cirrhosis, active hepatitis or significant fibrosis
(based on MRI or liver biopsy)
2. liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of
cirrhosis, active hepatitis or significant fibrosis
– Inadequate bone marrow function, as defined by an absolute neutrophil count of
<1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L. - Any contraindications to the use of 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. - Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment - Unable to receive red blood cell (RBC) transfusion. - Prior receipt of an allogeneic HSC transplant. - Prior receipt of gene therapy. - Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin. - Immediate family member with a known or suspected Familial Cancer Syndrome. - Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects. - Any other condition that would render the subject ineligible for HSCT. - Participation in another clinical study with an investigational drug within 30 days of screening.