Thalassemia Major
Conditions
Brief summary
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.
Detailed description
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.
Interventions
gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103
Sponsors
First Affiliated Hospital of Guangxi Medical University
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
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
* Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor. * Active bacterial, viral, or fungal infection. * Treated with erythropoietin prior 3 months. * Immediate family member with any known hematological tumor. * Subjects with severe psychiatric disorders to be unable to cooperate. * Recently diagnosed as malaria. * History of complex autoimmune disease. * Persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value \>3 X the upper limit of normal (ULN). * Subjects with severe heart, lung and kidney diseases. * With serious iron overload, serum ferritin\>5000mg/ml. * Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or Investigator. * Subjects who are receiving treatment from another clinical study, or have received another gene therapy. * Subjects or guardians had resisted the guidance of the attending doctor. * Subjects whom the investigators do not consider appropriate for participating in this clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3) | From 12 months to 24 months post transplant | 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 |
| 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 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| All-cause mortality | From 12 months to 24 months post transplant | — |
| Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3) | From 12 months to 24 months post transplant | Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months |
| Proportion of subjects achieving TR6 | 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 | — |
Other
| Measure | 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 |
Countries
China
Outcome results
None listed