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| Name | Class |
|---|---|
| First Affiliated Hospital of Guangxi Medical University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| γ-globin reactivated autologous hematopoietic stem cells | Experimental | each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| γ-globin reactivated autologous hematopoietic stem cells | Biological | gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion | From 12 months to 24 months post transplant | |
| Time to neutrophil engraftment | From 12 months to 24 months post transplant | |
| Time to platelet engraftment | From 12 months to 24 months post transplant | |
| Frequency and severity of adverse events through 100 days after BRL-103 Infusion | 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 | From 12 months to 24 months post transplant |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | From 12 months to 24 months post transplant |
| Proportion of subjects achieving TR6 |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in the proportion of red blood cells expressing HbF in the blood circulation | From 12 months to 24 months post transplant | |
| LDH levels over time | From 12 months to 24 months post transplant |
Key inclusion criteria:
Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent.
Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+、β
+β0, βEβ0 genotype.
Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV.
Subjects body condition eligible for autologous stem cell transplant.
Key exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| lai yongrong, PhD | First Affiliated Hospital of Guangxi Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Bioray Laboratories Inc | Shanghai | Shanghai Municipality | 200241 | China |
clinical study protocol will be shared after Estimated Primary Completion Date
data will be available before 2023.10.1, one week long
university and institute
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| ID | Term |
|---|---|
| D017086 | beta-Thalassemia |
| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
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| From 12 months to 24 months post transplant |
| Proportion of subjects achieving TR12 | From 12 months to 24 months post transplant |
| Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6) | From 12 months to 24 months post transplant |
| Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12) | From 12 months to 24 months post transplant |
| Incidence of transplant related mortality (TRM) within 100 days and within 1 year | 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. | From 12 months to 24 months post transplant |
| All-cause mortality | From 12 months to 24 months post transplant |
| Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time | From 12 months to 24 months post transplant |
| Fetal hemoglobin concentration (pre-transfusion) over time | From 12 months to 24 months post transplant |
| Total hemoglobin concentration (pre-transfusion) over time | From 12 months to 24 months post transplant |
| Change in serum ferritin level from baseline over time | From 12 months to 24 months post transplant |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |