Status:

ACTIVE_NOT_RECRUITING

Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major

Lead Sponsor:

Children's Hospital of Fudan University

Collaborating Sponsors:

CorrectSequence Therapeutics Co., Ltd

Conditions:

Beta-Thalassemia

Eligibility:

All Genders

3-17 years

Phase:

EARLY_PHASE1

Brief Summary

The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of base-edited autologous hematopoietic stem cell transplantation(CS-101) in treating patients with β-t...

Detailed Description

CS-101 is an autologous CD34+ cell suspension modified by ex vivo base editing technology, removing the inhibitory effect of BCL11A on the γ-globin coding gene, inducing the production of γ-globin cha...

Eligibility Criteria

Inclusion

  • 3 to 17 years old(inclusive) male or female subjects at the time of informed consenting
  • Diagnosis of β-thalassemia, genotypes include but are not limited to β+β0, βEβ0, β0β0, etc
  • Generally in good condition, Karnofsky performance score≥60 points for subjects≥16 years old at the time of autologous hematopoietic stem cell collection, or Lansky Play-Performance score≥60 points for subjects under 16 years old, or equivalent clinical evaluation as the investigator site's common practice
  • For female subjects of childbearing potential: use effective contraceptive measures for at least 1 month prior to screening and agree to continue using such measures for contraception throughout the study
  • For male subjects who have a potential ability to father a child: use condoms or other methods continuously from the start of mobilization to ensure effective contraception for sexual partners during the study period

Exclusion

  • Treatment with other investigational medications or other experimental interventions 30 days prior to signing informed consent or within 6 half-lives of the drug, whichever is longer.
  • Subjects who have received or are receiving thalidomide and/or Luspatercept, when their drug-drug interaction on the efficacy and safety of CS-101 cannot be ruled out, unless at least there are 3 test results showing the total hemoglobin level before transfusion is below 9g/dL in the past 6 months before screening.
  • Previously received allogeneic hematopoietic stem cell transplantation or gene(edited) therapy.
  • Subjects have available related fully matching donors and are eligible and prepared for allogeneic hematopoietic stem cell transplantation.
  • Subjects with coexisting α-thalassemia and more than 2 deletions or non-deletional mutations in the α-globin chain coding genes.
  • Known to be allergic to drugs used during autologous hematopoietic stem cell transplantation (including but not limited to granulocyte colony-stimulating factor, busulfan, dextran), excipients(such as dimethyl sulfoxide), or instruments(such as intravenous catheters) as determined by the investigator are deemed unsuitable to participate in this study.
  • Those with active infections, including but not limited to: HIV, hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr virus and treponema pallidum test positive, or known tuberculosis, parasitic infection, etc. who are judged by the investigator to be unsuitable to participate in this study
  • Echocardiography results with ejection fraction below 45%
  • Subjects who are febrile (temperature over 37.3° C) should be held back from enrolment.
  • Advanced liver disease, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) or baseline International Normalized Ratio (INR) \>1.5 × ULN
  • MRI during the screening period showed heavy iron overload and is judged by the investigator to be unable to participate in the study.
  • Patients with past/present history of cancer
  • Known neurological disorders, psychological problems or mental illness, and is judged by the investigator to be unable to cooperate with the study procedures
  • Known history of uncontrolled epileptic seizures and is judged by the investigator to be unfit to participate in this study
  • Known history of other serious cardiovascular, pulmonary, renal diseases, digestive tract conditions, liver diseases and / or other conditions, etc., and are judged by the investigator to be intolerable or inappropriate for autologous hematopoietic stem cell mobilization, collection, and myeloablative conditioning and infusion
  • Pregnant or lactating women

Key Trial Info

Start Date :

November 7 2023

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

September 30 2025

Estimated Enrollment :

5 Patients enrolled

Trial Details

Trial ID

NCT06065189

Start Date

November 7 2023

End Date

September 30 2025

Last Update

February 10 2025

Active Locations (1)

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Page 1 of 1 (1 locations)

1

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China, 201102