A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia
- Registration Number
- NCT06024876
- Lead Sponsor
- CorrectSequence Therapeutics Co., Ltd
- Brief Summary
The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of CS-101 in treating β-thalassemia.
- Detailed Description
CS-101 is an autologous CD34+ cell suspension, edited by ex vivo base editing technology, which modifies the BCL11A binding site in HBG promoter, so that it loses the ability to bind to BCL11A, which can re-induce the production of γ-globin chain and increase the concentration of fetal hemoglobin(HbF) in the blood, compensating for the function of missing adult hemoglobin HbA to achieve clinical cure. The therapy addresses two major challenges in the current treatment of the disease: lack of matching donors and graft-versus-host diseases in allogeneic hematopoietic stem cell transplantation.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 5
Not provided
- 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.
- 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%.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CS-101 CS-101 CS-101: Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique
- Primary Outcome Measures
Name Time Method Frequency and severity of adverse events(AEs）as assessed by CTCAE v5.0 From signing informed consent to 12 months post-CS-101 infusion Time to neutrophil and platelet engraftment Days post-CS-101 infusion 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； 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；
Incidence of transplant-related mortality From baseline to 100 days post-CS-101 infusion Proportion of subjects achieving transfusion independence for at least 6 consecutive months From 3 months up to 12 months post-CS-101 infusion Proportion of subjects with engraftment within 42 days post-CS-101infusion Subjects with engraftment is defined as neutrophil engrafted
All-cause mortality From signing informed consent to 12 months post-CS-101 infusion Time to last red blood cell(RBC) transfusion Days post-CS-101 infusion
- Secondary Outcome Measures
Name Time Method Change in total hemoglobin(Hb) concentration over time up to 12 months post-CS-101 infusion Total hemoglobin concentration change from baseline to 12 months post-CS-101 infusion
Change in fetal hemoglobin(HbF) concentration over time up to 12 months post-CS-101 infusion γ-globin concentration change from baseline to 12 months post-CS-101 infusion
Chimerism level in Peripheral blood and bone marrow up to 12 months post-CS-101 infusion Proportion of alleles with intended genetic modification in peripheral blood leukocytes and bone marrow over time
Trial Locations
- Locations (1)
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, China