- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06065189
Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major
Evaluation and Promotion of Key Technologies of Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major
Study Overview
Status
Conditions
Intervention / Treatment
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 chains, increasing the concentration of fetal hemoglobin (HbF) in the blood, compensating for the loss of adult hemoglobin (HbA) to treat transfusion-dependent type/ Major β - thalassemia. The therapy addresses two major challenges in the treatment of the disease: lack of matching donors and graft-versus-host responses commonly seen in allogeneic hematopoietic stem cell transplantation.
The study consists of the following five phases:
Screening phase: Sign informed consent, complete screening assessments, and confirm the eligibility for enrollment; Baseline: check the subject's baseline status; Mobilization, collection and manufacturing phase: mobilize, collect autologous CD34+ cells and manufacture, release and transport CS-101 product; Conditioning and treatment phase: including myeloablation and CS-101 product infusion; Follow-up phase: 180 days post-infusion.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Xiaowen Zhai, M.D.
- Phone Number: 862164931126
- Email: zhaixiaowendy@163.com
Study Contact Backup
- Name: Zifeng Li, M.S.
- Phone Number: +8613920704768
- Email: zfli18@fudan.edu.cn
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 6 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
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CS-101 injection
Autologous CD34+(cluster of differentiation 34) hematopoietic stem cell suspension modified by in vitro base editing technique
|
Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency and severity of adverse events(AEs) as assessed by CTCAE v5.0
Time Frame: From signing informed consent to 180 days post-CS-101 infusion
|
From signing informed consent to 180 days post-CS-101 infusion
|
|
Occurrence of engraftment
Time Frame: within 42 days post-CS-101 infusion
|
Subjects with engraftment is defined as neutrophil engrafted
|
within 42 days post-CS-101 infusion
|
Time to neutrophil and platelet engraftment
Time Frame: 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
|
Days post-CS-101 infusion
|
Occurrence of transplant-related death
Time Frame: baseline to 100 days post-CS-101 infusion
|
baseline to 100 days post-CS-101 infusion
|
|
Occurrence of all-cause death
Time Frame: From signing informed consent to 180 days post-CS-101 infusion
|
From signing informed consent to 180 days post-CS-101 infusion
|
|
Occurrence of achieving transfusion reduction for at least 3 consecutive months
Time Frame: From 3 months post -CS-101 infusion to 3 months post -CS-101 infusion
|
From 3 months post -CS-101 infusion to 3 months post -CS-101 infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to last red blood cell(RBC) transfusion
Time Frame: Days post-CS-101 infusion
|
Days post-CS-101 infusion
|
|
Occurrence of achieving transfusion independence for at least 3 consecutive months
Time Frame: From 3 months up to 180 days post-CS-101 infusion
|
From 3 months up to 180 days post-CS-101 infusion
|
|
Change in total hemoglobin(Hb) concentration over time
Time Frame: up to 180 days post-CS-101 infusion
|
up to 180 days post-CS-101 infusion
|
|
Change in fetal hemoglobin(HbF) concentration over time
Time Frame: up to 180 days post-CS-101 infusion
|
up to 180 days post-CS-101 infusion
|
|
Chimerism level in Peripheral blood and bone marrow
Time Frame: up to 180 days post-CS-101 infusion
|
Proportion of alleles with intended genetic modification in peripheral blood leukocytes and bone marrow over time
|
up to 180 days post-CS-101 infusion
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Xiaowen Zhai, M.D., Children's Hospital of Fudan University
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CS-101-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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