An Open-Label Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CD34+ Human Hematopoietic Stem Cells Modified Using Transformer Base Editor in Participants With Severe Sickle Cell Disease
The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of CS-101 injection in treating sickle cell disease.
• 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.