β Thalassemia Major
Conditions
Brief summary
This is a non-randomized, open label, single-dose, phase 1/2 study in up to 12 participants with β-thalassemia major.This study aims to 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 Crispr/Cas9 gene editing system. Subject participation for this study will be 1 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
Sponsors
Xiangya Hospital of Central South University
The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Fully understand and voluntarily sign informed consent. 5-15years old. At least one legal guardian and/or Subjects to sign informed consent. * Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, 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.
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 |
|---|---|---|
| Safety evaluation of γ-globin reactivated autologous hematopoietic stem cells | up to 24 months post transplant | Proportion of subjects with engraftment; Overall survival. |
| Incidence and severity of adverse events as a measure of safety and tolerability. Adverse events assessed according to NCI-CTCAE v5.0 criteria | up to 24 months post transplant | Incidence of AEs and SAEs post transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy evaluation of γ-globin reactivated autologous hematopoietic stem cells | up to 24 months post transplant | Proportion of subjects achieving transfusion independence for at least 6 months (TI6); Proportion of subjects achieving TI12; Proportion of alleles with intended genetic modification in bone marrow cells; Change in total hemoglobin concentration; Change from baseline in annualized frequency and volume of packed RBC transfusions. |
Countries
China
Outcome results
None listed