β-thalassemia Major
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 patients with β-Thalassemia Major
Detailed description
CS-101 is an autologous CD34+(Cluster of differentiation 34) cell suspension, edited by ex vivo base editing technology, which modifies the BCL11A binding site in HBG(Hemoglobin Subunit Gamma) 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 HbF(fetal hemoglobin) in the blood, compensating for the function of missing HbA(adult hemoglobin) 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
GENETICCS-101 injection
Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique
Sponsors
CorrectSequence Therapeutics Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily signed informed consent. Male or female participants aged 12 to 35 years (inclusive). The participant or their legally authorized representative must sign the informed consent. If the participant is under 18 years of age, their legally authorized representative must also sign the informed consent. * Diagnosed with β-thalassemia major (transfusion-dependent). Received at least 8 units of red blood cell transfusions within 12 months prior to screening, and documented hemoglobin level ≤ 70 g/L pre-transfusion. * Good general condition: Karnofsky score (≥16 years of age) ≥ 60, or Lansky Play-Performance score (\<16 years of age) ≥ 60. * For females of childbearing potential: From the start of the screening, highly effective contraception or complete abstinence (if this is their usual lifestyle), and agree to maintain such contraception throughout the study. * For males of childbearing potential: Use condoms or other methods to ensure effective contraception for sexual partners continuously from mobilization through the study period.
Exclusion criteria
* Received other investigational products or other experimental interventions within 30 days prior to signing informed consent or within 6 elimination half-lives of the drug (whichever is longer). * Received or is receiving thalidomide, hydroxyurea, and/or luspatercept within 3 months prior to screening. * Previous received allogeneic hematopoietic stem cell transplantation, gene therapy, or gene-editing therapy; or participants who can be maintained with standard therapy. * Participants with a matched sibling donor, or with a matched unrelated / haploidentical related donor and judged by the investigator to have no high-risk factors for allogeneic hematopoietic stem cell transplantation. * Participants with coexisting α-thalassemia with more than 2 α-globin chain gene deletions or non-deletional mutations. * Known hypersensitivity to drugs used during autologous hematopoietic stem cell transplantation, excipients, or devices, judged by the investigator to be ineligible for this study. * Infection with HIV, cytomegalovirus, Epstein-Barr virus, or Treponema pallidum during screening; active HBV or HCV infection (participants with stable hepatitis B after treatment (HBV-DNA negative) and cured hepatitis C (HCV-RNA negative) may be included). Known active bacterial, viral, fungal, or parasitic infection. * Echocardiographic ejection fraction \< 50%. * Laboratory abnormalities: AST or ALT \> 3 × upper limit of normal (ULN); or International normalized ratio (INR) \> 1.5 × ULN. * Cardiac severe iron overload detected by MRI during screening, judged by the investigator to be unsuitable for hematopoietic stem cell transplantation. * Current or history of malignancy. * Participants with known neurological consciousness disorders, psychological problems, or psychiatric diseases judged by the investigator to be unable to comply with study procedures. * Participants with known history of uncontrolled seizures judged by the investigator to be ineligible for this study. * Uncontrolled bleeding disorders. * Leukocyte count \< 3 × 10⁹/L and/or platelet count \< 100 × 10⁹/L not due to hypersplenism. * Participants with other severe cardiovascular, pulmonary, renal, gastrointestinal, hepatic diseases, and/or other organ disorders judged by the investigator to be ineligible for this study. * Pregnant or lactating females; females of childbearing potential with a positive serum pregnancy test. * Received live or live-attenuated vaccine within 90 days prior to myeloablation. * Participants with autoimmune diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs(Adverse Events) and SAEs(Serious Adverse Events) after CS-101 infusion | Up to 16 months post-CS-101 infusion | Frequency and severity of adverse events(AEs）as assessed by CTCAE(Common Terminology Criteria for Adverse Events)v5.0 |
| Overall survival | Up to 16 months post-CS-101 infusion | — |
| Proportion of Subjects with engraftment | Within 42 days post-CS-101 infusion | Subjects with engraftment is defined as neutrophil engrafted |
| Time to neutrophil engraftment | Up to 16 months post-CS-101 infusion | — |
| Time to platelet engraftment | Up to 16 months post-CS-101 infusion | — |
| Incidence of transplant-related mortality | Up to 100 days post-CS-101 infusion | — |
| Proportion of subjects achieving transfusion independence for at least 12 consecutive months | Up to 16 months post-CS-101 infusion | Maintaining transfusion independence for at least 12 consecutive months while maintaining a weighted mean hemoglobin≥90g/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving transfusion independence for at least 6 consecutive months | Up to 16 months post CS-101 Infusion | Maintaining transfusion independence for at least 6 consecutive months while maintaining a weighted mean hemoglobin≥90g/L |
| Changes in targeted editing efficiency in peripheral blood nucleated cells over time | Up to 16 months post CS-101 infusion | — |
| Changes in targeted editing efficiency in bone marrow nucleated cells over time | Up to 16 months post CS-101 infusion | — |
| Change in fetal hemoglobin(HbF) concentration over time | Up to 16 months post CS-101 infusion | — |
| Change in total hemoglobin(Hb) concentration over time | Up to 16 months post CS-101 infusion | — |
Countries
China
Contacts
CONTACTXiaokai Li
CONTACTYaliang Li
Outcome results
None listed