CS-206 in Patients With Sickle Cell Disease

Inclusion criteria

• Participants must be between 12 to 35 years old (inclusive). Participants or their legal guardians (for participants below 18 years old) must provide written informed consent before any study-related procedures.
• Participants must have a Documented βS/βS, βS/β0 or βS/β+ genotype.
• Participants must have at least one of the following conditions
• At least 2 occurrences of any of the following events within 2 years prior to screening.
• Acute pain crisis: requiring a visit to a medical facility and administration of pain medications (opioids or intravenous NSAIDs) or red blood cell transfusions.
• Acute chest syndrome: defined by the presence of a new pulmonary infiltrate on a chest X-ray, associated with pneumonia-like symptoms, including chest pain, fever, or respiratory distress.
• Priapism lasting more than 2 hours and necessitating a visit to a medical facility for intervention.
• Stroke or transient ischemic attack (TIA): confirmed by imaging studies (e.g., MRI or CT scan), including silent stroke, and overt stroke leading to neurological deficits lasting \>24 hours.
• Presence of red cell alloimmunization (\>2 antibodies) and the need for ongoing chronic transfusions.
• Participants who have failed, not tolerated, refused the standard of care for Sickle Cell Disease (SCD), or are unable to access the standard of care due to the availability
• Other situations deemed appropriate for hematopoietic stem cell transplantation according to the sickle cell anemia treatment guidelines, as determined by the investigator.
• Laboratory Parameters:
• Documented Hemoglobin S (HbS) level ≥30% of total hemoglobin (Hb) concentration prior to transfusion.
• HbF at screening \< 20%
• Participants must have a Karnofsky Performance Status (KPS for participants above 16 years old, inclusive) or Lansky Play-Performance Scale (LPPS for participants below 16 years old) score of ≥70, indicating sufficient functional status to undergo the intervention.
• Willing to comply with the protocol requirements, use contraception as required, attend regular follow-up visits, and cooperate with examinations.

Exclusion criteria

• Female participants who are pregnant, breastfeeding, or planning pregnancy during the study period are excluded.
• Participation in another investigational drug trial within 30 days prior to screening or within 5 half-lives (whichever is longer).
• Subjects who have received or are receiving luspatercept treatment within 3 months prior to screening.
• Subjects who have previously received any gene therapy for the disease.
• Subjects with a fully matched related donor who are already scheduled for allogeneic hematopoietic stem cell transplantation.
• More than 10 unplanned hospitalizations or emergency visits within 12 months prior to screening, which the investigator believes are related to significant chronic pain rather than acute pain crisis (VOC).
• Severe liver dysfunction:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3× the upper limit of normal (ULN) or:
• International Normalized Ratio (INR) \>1.5× ULN
• Severe renal impairment (creatinine clearance \<30 mL/min/1.73 m²) are excluded.
• Subjects with HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), or Treponema pallidum infection during the screening period; those with active HBV or HCV infection; or known tuberculosis or parasitic infection, etc. Excludes subjects with stable hepatitis B (HBV-DNA negative) after treatment and those cured of hepatitis C (HCV-RNA negative). Known active bacterial, viral, or fungal infections.
• Deemed unsuitable for autologous hematopoietic stem cell transplantation procedures as determined by the investigator.
• Other situations deemed unsuitable for this study as determined by the investigator.