the safety and efficacy evaluation of hgi-001 injection in patients with transfusion-dependent β-thalassemia

Conditions: β-thalassemia

Summary: this is an open label study to evaluate the safety and efficacy of β-globin restored autologous hematopoietic stem cells in ß-thalassemia major patients

we will recruit ß-thalassaemia major patients and collect their autologous hematopoietic stem cells, which will be modified with the lentihbbt87q system to restore β-globin expression. after conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.

Eligibility criteria:
inclusion criteria: 1. aged 18-35 years (inclusive), icf can be provided by the patient and/or legal guardian; 2. definitively diagnosed with severe tdt without genotype restriction, and a valid test report can be provided; 3. average transfusion volume \> 100 ml/kg/year or transfusion frequency \> 8 times/year within 2 years prior to enrollment, or has been definitively diagnosed with tdt; 4. at least 3 months of full volume transfusion (verification of blood transfusion records can be provided) prior to screening, and hb is maintained at ≥ 9.0 g/dl; 5. ferritin load \< 3000 μg/l, cardiac and liver iron indicates moderate or lesser iron overload; records of iron chelation treatments within 3 months before screening (including prescription or receipt) can be provided; 6. acceptable organ functions (including heart, liver, kidney, lung and coagulation functions), stable disease condition, and suitable for busulfan pre-treatment and hematopoietic stem cell (hsc) transplantation as judged by the investigator; 7. meets follow-up requirements, adheres to treatment arrangements, and is able to return to the hospital regularly to undergo various examinations within 2 years after reinfusion of hgi-001 injection. exclusion criteria: 1. patients with fully hla-matched donors; 2. received allogeneic transplantation, which needs to be weighed and evaluated by an expert committee; received other gene therapies; 3. have previously undergone splenectomy; 4. uncorrected bleeding disorder; 5. uncontrolled epilepsy and mental illness; 6. received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment; 7. psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment; 8. patients with pulmonary hypertension who have not been given effective intervention; 9. persistent toxicity (≥ ctcae grade 2) induced by previous treatment; 10. positive for anti-rbc antibodies in antibody screening; 11. positive for hepatitis b surface antigen (hbsag) and hbv dna copy number \> upper limit of normal (uln) (hbv dna test not required for patients negative for hbsag), positive for hepatitis c virus (hcv) antibody, positive human immunodeficiency virus (hiv), or positive for treponema pallidum antibody (tp-ab) (subjects who are positive for the antibody due to vaccination can be enrolled). in certain clinical environments/regions, subjects who are positive for other tests can also be excluded from the trial, such as, human lymphocytic virus-1 (htlv-1) or -2 (htlv-2), tuberculosis, and toxoplasmosis. 12. has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease; 13. immediate family member with or suspected of having a familial cancer (including but not limited to hereditary breast and ovarian cancers, nonpolyposis colorectal cancer, and adenomatous polyposis); 14. severe bacterial, viral, fungal or parasitic infection; 15. other illnesses which render the subject unsuitable for participation (e.g., severe liver, kidney or heart disease); definition of severe liver and kidney disease: a. aspartate aminotransferase (ast), alanine aminotransferase (alt), or total bilirubin \> 3 × uln; b. liver magnetic resonance imaging (mri) indicates significant cirrhosis; c. liver biopsy indicates cirrhosis, severe fibrosis or active hepatitis (liver biopsy is only performed when liver mri indicates active hepatitis and significant fibrosis without evidence for cirrhosis); d. creatinine clearance \< 30% of normal; 16. wbc \< 3 × 109/l and/or plt \< 100 × 109/l; 17. has diabetes, abnormal thyroid functions or other endocrine disorder; 18. participated in other interventional clinical studies within 4 weeks before the trial; 19. poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.