9 United States sites
12 to 50 Years
Phase 1/Phase 2
1. Be ≥12 and ≤50 of age at time of consent.
2. Diagnosis of sickle cell disease (SCD), with either βS/βS or βS/β0 or βS/β+ genotype.
3. Have severe SCD. i.e., in the setting of appropriate supportive care measures for SCD
(e.g.,pain management plan) have experienced at least 4 severe VOEs in the 24 months
prior to informed consent.
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.
4. Karnofsky performance status of ≥ 60 (≥16 years of age) or a Lansky performance status
of ≥60 (<16 years of age). 5. Have either experienced hydroxyurea (HU) failure at any point in the past or must have intolerance to HU (defined as patient being unable to continue to take HU per PI judgement). 6. Have been treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on SCD history.
1. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2),
hepatitis B virus (HBV), or hepatitis C (HCV).
2. Clinically significant and active bacterial, viral, fungal, or parasitic infection.
3. Inadequate bone marrow function, as defined by an absolute neutrophil count of < 1000/µL (< 500/µL for subjects on HU treatment) or a platelet count < 120,000/µL (without hypersplenism). 4. Any history of severe cerebral vasculopathy: defined by overt or hemorrhagic stroke; abnormal transcranial Doppler [≥200 cm/sec] needing chronic transfusion; or occlusion or stenosis in the polygon of Willis; or presence of Moyamoya disease. Subjects with radiologic evidence of silent infarction in the absence of any of the above criteria would still be eligible 5. Advanced liver disease, defined as: 1. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value >3× the upper limit of normal (ULN), or
2. Baseline prothrombin time or partial thromboplastin time >1.5× ULN, suspected of
arising from liver disease, or
3. Magnetic Resonance Imaging (MRI) of the liver demonstrating clear evidence of
4. MRI findings suggestive of active hepatitis, significant fibrosis, inconclusive
evidence of cirrhosis, or liver iron concentration ≥15 mg/g require follow-up
liver biopsy in subjects ≥18 years of age. In subjects <18 years of age, these MRI findings are exclusionary, unless in the opinion of the Investigator, a liver biopsy could provide additional data to confirm eligibility and would be safe to perform. If a liver biopsy is performed based on MRI findings, any evidence of cirrhosis, bridging fibrosis, or significant active hepatitis will be exclusionary. 6. 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. 7. Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin. 8. Prior receipt of an allogeneic transplant. 9. Immediate family member with a known or suspected Familial Cancer Syndrome. 10. Diagnosis of significant psychiatric disorder of the subject that, in the Investigator's judgment, could seriously impede the ability to participate in the study. 11. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. 12. Participation in another clinical study with an investigational drug within 30 days of Screening. 13. Prior receipt of gene therapy. 14. Patients needing curative anticoagulation therapy during the period of conditioning through platelet engraftment (patients on prophylactic doses of anticoagulants are eligible). 15. Unable to receive RBC transfusion.