Beta-Thalassemia Beta-Thalassemia
Conditions
Interventions
an autologous CD34+ cell-enriched population that contains hematopoietic stem cells (HSCs) transduced with lentiviral vector (named LentiHBBT87Q) encoding the Beta A-T87Q-globin gene.
Experimental Biological/Vaccine
HGI-001
Sponsors
Hemogen HongKong Alpha Technology, Ltd
Eligibility
Sex/Gender
All
Age
13 Years to 18 Years
Inclusion criteria
Inclusion criteria: 1 Subjects between 13 and 18 years of age at the time of consent and are able to provide written informed consent 2 Diagnosis of TDT also known as Beta-thalassemia major without genotype restriction and a valid test report can be provided 3. A history of at least 100 mL per kg per year of pRBCs transfusion or greater than or equal to 8 transfusions of pRBCs per year for the previous 2 years 4. Sufficient blood transfusion for at least 3 months before screening or transfusion records can be provided and Hb is maintained at greater than or equal to 9.0 g per dL before each transfusion. 5. The level of serum ferritin less 3000ng per mL Cardiac magnetic resonance imaging (MRI) T2 more than 10ms and Liver MRI T2 more than 1.4ms or LIC value less 15mg per g dry weight 6. Clinically stable and eligible for autologous hematopoietic stem cell transplant (HSCT) 7. Adequate organ function for conditioning with busulfan 8. Treated and followed for at least 2 years in a specialized hospital or Subjects are eligible for follow up and comply with the clinical trial schedule of assessments
Exclusion criteria
Exclusion criteria: 1. A known and available human leukocyte antigen (HLA)-matched donor. 2. Prior receipt of HSCT or gene therapy. 3. A history of splenectomy. 4. Uncorrected bleeding disorder 5. Uncontrolled epilepsy or mental disorders 6. Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment. 7. Presence of psychoactive substance, drug, or alcohol abuse within six months prior to screening. 8. Pulmonary hypertension without effective intervention. 9. Persistent toxicity (Greater than or equal to CTCAE grade 2) induced by previous treatment. 10. Positive for anti-RBC antibodies. 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 for 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 a known or suspected Family Cancer Syndromes (for example hereditary breast and ovarian cancers syndrome, hereditary nonpolyposis colorectal cancer, and adenomatous polyposis) 14. Clinically significant and active bacterial, viral, fungal, or parasitic infection. 15. Subjects with other medical conditions who are not eligible to participate in the study (e.g., severe liver, kidney, or heart disease, etc.) Advanced liver disease a) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin more than 3 X the upper limit of normal (ULN) b) MRI of the liver indicating clear evidence of cirrhosis c) Liver biopsy suggests active hepatitis, significant fibrosis, conclusive evidence of cirrhosis (Liver biopsy is only carried out when MRI findings suggestive of active hepatitis, significant fibrosis, inconclusive evidence of cirrhosis). 16. White blood cell (WBC) less 3 x 10*9/L and/or PLT less 100 x 109/L. 17. Subjects with diabetes, abnormal thyroid functions or other endocrine disorders. 18. Participated in other interventional clinical studies within 4 weeks prior to the trial. 19. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. 20. An assessment by the investigator that the subject would not comply with study procedures outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Hematopoietic stem cell engraftment success. 1, 2, 3, 6, 9, 12 months Adverse events and serious adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| 2. Transplant-related mortality and disabling events do not occur within 100 days and 365 days respectively, after HGI-001 Injection refusion. 1, 2, 3, 6, 9, 12 months Adverse events and serious adverse events,3. Overall survival during the clinical trial. 1, 2, 3, 6, 9, 12 months Overall survival | — |
Countries
Thailand
Contacts
Public ContactKanya Suphapeetiporn
Faculty of Medicine, Chulalongkorn University
Outcome results
None listed