iHSCs With the Gene Correction of HBB Intervent Subjests With β-thalassemia Mutations

Study Overview
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Brief Summary
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This is a single centre、single arm、open-label study，to investigate the safety and efficacy of the gene correction of HBB in patient-specific iHSCs using CRISPR/Cas9.

Detailed Description
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The purpose of this study is to evaluate the efficacy and safety of transplantation iHSCs intervent subjests with β-thalassemia mutations.

Official Title
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A Safety and Efficacy Study of a Single Center, Open-label, Single Arm About the Gene Correction of HBB in Patient-specific iHSCs Using CRISPR/Cas9 That Intervent Subjests With β-thalassemia Mutations

Conditions
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Thalassemia

Intervention / Treatment
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* Biological: iHSCs treatment group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ≥ 2 and ≤ 60 years of age Subjects was confirmed the transfusion-dependent β-thalassemia Adequate organ function, as defined by: Serum creatinine ≤ 1.5 mg/dl ； Serum ALT/AST）≤2.5×ULN；ALB≥25g/L； Serum total bilirubin < 1.5x ULN Left ventricular ejection fraction≥50% Chest X-ray and ecg test results were normal, no serious cardiopulmonary diseases Subjects survival was expected≥6 months Adult patients were willing to use reliable contraceptives (such as condoms) and not to donate sperm throughout the study period and within three months of discharge Subjects and the guardians able to undergo post-physical therapy/rehabilitation Exclusion Criteria: Subjects allergic to macromolecular biological agents such as antibodies or cytokines Subjects receipt of any investigational clinical trials within 3 months. Subjects previous treatment with any hematopoietic stem cell transplantation or other organ transplantation Uncontrolled bleeding symptoms Severe cardiovascular disease is known, including any of the following: Myocardial infarction or thrombosis has occurred in the past six months Subjects with unstable angina pectoris Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification Subjects have one kinds of tumors within 5 years Active hepatitis B (HBV DNA>1000copy/mL), hepatitis C or HIV infection. Subjects have an infectious diseases that cannot be controlled within 4 weeks subjects have severe central nervous system disease or epilepsy Subjects are Suffering from mental illness; Patients with alcohol dependence, drug abuse, drug addiction, and medical, psychological or social conditions that may interfere with research or have an impact on the evaluation of research results Women in pregnancy (positive urine/blood pregnancy test) or lactation Subjects who have other conditions that were not appropriate for the group determined by the researchers.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 60 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iHSCs treatment group<br> | Biological: iHSCs treatment group<br>* iHSCs intravenous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment related adverse events as assessed by CTCAE v4.0 | Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment | 1 year |