the Safety and Efficacy Evaluation of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia

Prior treatment

• Received allogeneic transplantation, which needs to be weighed and evaluated by an expert committee; received other gene therapies;
• Have previously undergone splenectomy;
• Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
• Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
• Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment;
• Positive for anti-RBC antibodies in antibody screening;
• Participated in other interventional clinical studies within 4 weeks before the trial;

Other illness

• Uncorrected bleeding disorder;
• Uncontrolled epilepsy and mental illness;
• Patients with pulmonary hypertension who have not been given effective intervention;
• Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
• 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);
• Severe bacterial, viral, fungal or parasitic infection;
• Has diabetes, abnormal thyroid functions or other endocrine disorder;
• Poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.

Lab values

• 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.
• 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;
• WBC \< 3 × 109/L and/or PLT \< 100 × 109/L;

Other

• Patients with fully HLA-matched donors;

• Aged 18-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
• Definitively diagnosed with severe TDT without genotype restriction, and a valid test report can be provided;
• 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;
• 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;
• 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;
• 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;
• 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.