This is a single arm, open label, single-dose, phase 1/2 study in up to 5 participants with β-thalassemia major.The study will evaluate the safety and efficacy of the treatment with γ-globin reactivated autologous hematopoietic stem cells in subjects with β-thalassemia major.
γ-globin reactivated autologous hematopoietic stem cells will be manufactured using Glycosylase Base Editors. Subject participation for this study will be 2 year. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 15 years post-transplant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103
Shanghai Bioray Laboratories Inc
Shanghai, Shanghai Municipality, China
Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
Time frame: From 12 months to 24 months post transplant
Time to neutrophil engraftment
Time frame: From 12 months to 24 months post transplant
Time to platelet engraftment
Time frame: From 12 months to 24 months post transplant
Frequency and severity of adverse events through 100 days after BRL-103 Infusion
Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
TR3 was defined as at least a 50% reduction in monthly red blood cell transfusion volume and transfusion frequency compared to baseline for at least 3 months
Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)
Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months
Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving TR6
Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving TR12
Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)
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Time frame: From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)
Time frame: From 12 months to 24 months post transplant
Incidence of transplant related mortality (TRM) within 100 days and within 1 year
Time frame: From 12 months to 24 months post transplant
Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.
Time frame: From 12 months to 24 months post transplant
All-cause mortality
Time frame: From 12 months to 24 months post transplant
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
Time frame: From 12 months to 24 months post transplant
Fetal hemoglobin concentration (pre-transfusion) over time
Time frame: From 12 months to 24 months post transplant
Total hemoglobin concentration (pre-transfusion) over time
Time frame: From 12 months to 24 months post transplant
Change in serum ferritin level from baseline over time
Time frame: From 12 months to 24 months post transplant