β-globin Restored Autologous HSC in β-thalassemia Major Patients

Study Overview
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Brief Summary
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This is a single center, single arm, open-label study to determine the safety and efficacy of β-globin restored autologous hematopoietic stem cells in β- thalassemia major patients with CVS-654 mutation.

Detailed Description
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β-globin restored 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.

Official Title
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a Safety and Efficacy Study of β-globin Restored Autologous Hematopoietic Stem Cells for β-thalassemia Major Patients With CVS-654 Mutation

Conditions
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β-thalassemia Major

Intervention / Treatment
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* Biological: β-globin restored autologous HSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 5-15 years old. Clinically diagnosed as β-thalassemia major with IVS-654 gene mutation phenotype; Subjects or at least one legal guardian/agent understand and voluntarily sign informed consent. 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. 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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: β-globin restored autologous HSC<br>each subject will accept one dose of β-globin restored autologous hematopoietic stem cells | Biological: β-globin restored autologous HSC<br>* gene edited autologous hematopoietic stem cells with β-globin restoration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with engraftment; |  | up to 42 days post transplant | 
| 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 60 days post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving transfusion independence; |  | up to 24 months post transplant | 
| Proportion of subjects with a > = 50% reduced annualized volume of packed RBC transfusions. |  | up to 24 months post transplant |