Evaluation and Promotion of Key Technologies of Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major

CS-101-03

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-thalassemia major.

2023-11-07

2024-10-16

2024-12-31

Recruiting

Early phase I

5

Inclusion Criteria: * 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 Criteria: * 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

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 5, 'type': 'ESTIMATED'}}

2024-05-01