A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)

Prior treatment

• Prior HSCT or contraindications to autologous HSCT
• Any prior or current malignancy or immunodeficiency disorder

Other illness

• Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells (HSCs) 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
• Any history of severe cerebral vasculopathy
• Advanced liver disease
• Immediate family member with a known or suspected Familial Cancer Syndrome
• Clinically significant and active bacterial, viral, fungal, or parasitic infection
  • Other protocol defined inclusion/exclusion criteria may apply

Other

• Available 10/10 HLA-matched related donor
• Unable to receive red blood cell (RBC) transfusion for any reason
• Unable or unwilling to comply with standard of care changes in background medical treatment in preparation of, during, or following HSCT, including and not limited to discontinuation of hydroxyurea, voxelotor, crizanlizumab, or L-glutamine
• Inadequate end organ function

• Diagnosis of severe sickle cell disease as defined by:
• Documented SCD genotype (βS/βS, βS/β0, βS/β+, or others) and
• History of at least two severe vaso-occlusive events per year requiring medical attention despite hydroxyurea or other supportive care measures in the two year-period prior to provision of informed consent or assent, as applicable
  • Karnofsky (for subjects \>16 years of age) or Lansky (for subjects ≤ 16 years of age) Performance Status ≥ 80%
  • Normal transcranial doppler velocity in subjects 16 years of age or younger