Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells
- Conditions
- β Thalassemia Major
- Interventions
- Biological: γ-globin reactivated autologous hematopoietic stem cells
- Registration Number
- NCT04211480
- Lead Sponsor
- Bioray Laboratories
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description γ-globin reactivated autologous hematopoietic stem cells γ-globin reactivated autologous hematopoietic stem cells each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
Shanghai Bioray Laboratories Inc.
🇨🇳Shanghai, Shanghai, China