Patients with transfusion-dependent beta-thalassemia (TDT) Thalassemia
Conditions
Interventions
HGI-001 Injection: an autologous CD34+ cell-enriched population that contains hematopoietic stem cells (HSCs) transduced with lentiviral vector (named LentiHBBT87Q) encoding the BetaA-T87Q globin gene
Experimental Drug
Sponsors
Hemogen HongKong Alpha Technology, Ltd
Eligibility
Sex/Gender
All
Age
18 Years to 35 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all the following criteria to be eligible for inclusion in this trial (1) Subjects between 18 and 35 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/kg/year of pRBCs transfusion or greater-than/equal to 8 transfusions of pRBCs per year for the previous 2 years. (4) Sufficient blood transfusion for at least 3 months before screening (transfusion records can be provided), and Hb is maintained at greater-than/equal to 9.0 g/dL before each transfusion. (5) The level of serum ferritin less than 3000 ng/mL, Cardiac magnetic resonance imaging (MRI) T2 more than 10 ms and Liver MRI T2 more than 1.4 ms (LIC value less than 15mg/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 (Subjects are eligible for follow-up, and complies with the clinical trial schedule of assessments).
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will not be eligible to participate in the study: Related to past treatments (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/equal to CTCAE grade 2) induced by previous treatment. (10) Positive for anti-RBC antibodies. Related to subject health (11) Positive for hepatitis B surface antigen (HBsAg) and HBV DNA copy number more than 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 times of 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). Severe kidney disease, defined as: creatinine clearance rate less than 30 percent of normal; (16) White blood cell (WBC) less than 3 x 10 9/L and/or PLT less than 100 x 10 9/L. (17) Subjects with diabetes, abnormal thyroid functions or other endocrine disorder. Others (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. (21) In case of insufficient cell for HGI-001 injection manufacturing (less than 6 x10 6/kg) after 2 cycles of mobilizations and for backup cell (less than 2 x 10 6/kg) collected after 2 cycles of mobilizations and bone marrow collection, subject may be withdrawn from the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hb Greater-than or equal to Hb 12 months during the study after HGI-001 Injection infusion Weighted average Hb greater-than or equal to 9 g/dL | — |
Secondary
| Measure | Time frame |
|---|---|
| VCN At 12 months during the study after HGI-001 Injection infusion Average VCN more than 0.1 in peripheral blood mononuclear cells,HbAT87Q At 12 months during the study after HGI-001 Injection infusion Average expression of HbAT87Q more than 2.0 g/dL,Nadir Hb During period of TI Weighted average nadir Hb,Characterization of transfusion reduction (TR) NA Change in average annual transfusion volume or frequency from baseline or change in percentage,Subjects who do not require transfusion NA Number of subjects who do not require transfusion for at least 6 consecutive months after treatment of HGI-001 Injection and have a weighted average Hb of greater-than or equal to 9.0 g/dL,Transfusion-free survival NA A subject meets the TI criteria and maintains transfusion-free survival,VCN and HbAT87Q expression NA Changes in VCN and HbAT87Q expression | — |
Countries
Thailand
Contacts
Public ContactJinhui Huang
Hemogen Therapeutic Co,.LTD
Outcome results
None listed