CS-206 in Patients With Sickle Cell Disease

NCT07000318 | Not Yet Recruiting Early Phase 1

• 1 other identifier: CS-206-02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of CS-206 injection in treating sickle cell disease.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (6)

• AEs(Adverse Events) and SAEs(Serious Adverse Events) after CS-206 infusion

  Frequency and severity of adverse events(AEs#as assessed by CTCAE(Common Terminology Criteria for Adverse Events)v5.0

  From signing informed consent to 24 months post-CS-206 infusion

• Incidence of transplant-related mortality

  Incidence of transplant-related mortality(Transplant-related mortality events defined as deaths assessed by the investigator as potentially transplant-related)

  From baseline to 100 days and 12 months post-CS-206 infusion

• Time to neutrophil engraftment

  Time to neutrophil engraftment is defined as first day of 3 consecutive measurements of absolute neutrophil count≥0.5×10\^9/L on three different days.

  Up to 24 months post-CS-206 infusion

• Time to platelet engraftment

  Time to platelet engraftment is defined as first day of 3 consecutive measurements of absolute platelet count≥20×10\^9/ L on three different days and without platelet transfusion.

  Up to 24 months post-CS-206 infusion

• All-cause mortality

  Up to 24 months post-CS-206 infusion

• Free from severe VOCs for 12 consecutive months (VF12)

  Whether the patient remained free from severe vaso-occlusive crises (VOCs) for 12 consecutive months (VF12)

  starting 60 days after the last red blood cell transfusion up to 24 months

Secondary Outcomes (6)

• Free from hospitalization due to severe vaso-occlusive crises for 12 consecutive months(HF12)

  starting 60 days after the last red blood cell transfusion up to 24 months

• Free from severe VOCs for 9 consecutive months (VF9)

  starting 60 days after the last red blood cell transfusion up to 24 months

• Annualized incidence of severe vaso-occlusive crises (VOC)

  starting 60 days after the last red blood cell transfusion up to 24 months

• Annualized incidence of hospitalization due to severe vaso-occlusive crises

  starting 60 days after the last red blood cell transfusion

• HbF (fetal hemoglobin) level in blood samples

  up to 24 months post-CS-206 infusion

Study Arms (1)

CS-206

EXPERIMENTAL

Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique

Genetic: CS-206

Interventions

CS-206 GENETIC

Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique

CS-206

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must be between 12 to 18 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Xiaowen Zhai, M.D.

  Children's Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaowen Zhai, M.D.

CONTACT

+86-021-64931126; zhaixiaowendy@163.com

Zifeng Li, M.S.

CONTACT

+86-13920704768; zfli18@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2025
• First Posted: June 2, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 2, 2025

Record last verified: 2025-05

Locations

CN (1)