Beta-Thalassemia
Conditions
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.
Interventions
BIOLOGICALCS-101
Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique
Sponsors
CorrectSequence Therapeutics Co., Ltd
First Affiliated Hospital of Guangxi Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria： * 6 to 35 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 * History of at least≥8 units/year of packed RBC transfusions in the prior 12 months prior to the screening period * 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 Key
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 in the past 7 days； |
| Proportion of subjects with engraftment | within 42 days post-CS-101infusion | Subjects with engraftment is defined as neutrophil engrafted |
| Incidence of transplant-related mortality | From baseline to 100 days post-CS-101 infusion | — |
| All-cause mortality | From signing informed consent to 12 months 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 | — |
| Time to last red blood cell(RBC) transfusion | Days post-CS-101 infusion | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | fetal hemoglobin 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 |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYongrong Lai, M.D.
First Affiliated Hospital of Guangxi Medical University
Outcome results
None listed