Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease

A Phase I/II Study of Nula-cel in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease

This study is a first-in-human, single-arm, open-label Phase I/II study of nula-cel in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.

Participants diagnosed with severe SCD will receive nula-cel via IV infusion following myeloablative conditioning in an autologous HSCT setting.

Inclusion Criteria:

• ≥12 to ≤ 40 years
• Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:
• recurrent severe VOC (≥ 4 episodes in the preceding 2 years)
• ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)
• Lansky/Karnofsky performance status of ≥ 80

Exclusion Criteria:

• Available 10/10 HLA-matched sibling donor
• Prior HSCT or gene therapy
• Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder
• Clinically significant and active bacterial, viral, fungal or parasitic infection
• Pregnancy or breastfeeding in a postpartum female
• Presence of a chromosomal abnormality/mutation that may put the participant at an increased risk for MDS or AML per investigator's judgment