A Study Evaluating the Safety and Efficacy of LentiRed Drug Product in Transfusion-dependent β-Thalassemia [TDT]

Subject participation for this study will be 5 years.

Inclusion criteria

• The subject himself/herself or one legal guardian/agent of the subject is required to fully understand the study and voluntarily sign a written informed consent.
• Ages 5 to 35, no gender limitation.
• The clinical diagnosis of TDT includes β0/β0, β+/β0, βE/β0 and β+/β+ genotypes. TDT was defined as severe anemia in patients with thalassemia (Hb persistent <70 g/L), regular RBC transfusion and standard iron removal therapy to survive for life.
• Karnofsky Level of Performance (KPS) score ≥70 in adult subjects and Lansky Level of Performance (LPS) score ≥70 in children subjects.
• Subjects were determined to undergo autologous hematopoietic stem cell transplantation by the principle investigator.
• Subjects must have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion criteria

• Hepatitis B virus (HBV) : HbsAg or HbcAb positive, nucleic acid test positive; Hepatitis C virus (HCV) : HCAb positive, nucleic acid test positive; Positive for Human immunodeficiency virus (HIV) antibody or Treponema pallidum (TP) specific antibody; Tuberculosis: positive interferon gamma release test.
• A white blood cell (WBC) count <3×10^9/L and/or platelet count <100×10^9/L, splenectomy was performed before.
• Uncured bleeding abnormalities.
• Any previous or current malignancy, myeloproliferative disease, or immune deficiency disease.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndromes, hereditary non-polyposis colorectal cancer syndromes and familial adenomatous polyposis).
• Previous hematopoietic stem cell transplantation (HSCT).
• Advanced liver disease, defined as: 1) Baseline alanine aminotransferase (ALT) or direct bilirubin ≥3 normal upper limit (ULN), or 2) Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or acute hepatitis.
• Baseline estimated glomerular filtration rate (eGFR) < 70 mL/min /1.73 m2, as determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation for ≥18 years of age, and Besides Schwartz Equation calculator < 18 years of age.
• Uncontrolled seizure disorder.
• Diffusion capacity of Carbon monoxide dispersion (DLco) <50% of predicted (corrected for hemoglobin and or alveolar ventilation, as clinically indicated ).
• A cardiac T2* <20 ms by magnetic resonance imaging (MRI).
• Severe iron overload, which in the opinion of the physician is grounds for exclusion.
• Clinically significant pulmonary hypertension.
• Participation in another clinical study with an investigational drug within 30 days of screening.
• Failure to obtain appropriate informed consent.
• Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator.
• Contraindications to the conditioning regimen.
• Prior receipt of genetic stem cell therapy.
• Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
• Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. Females of child-bearing potential are required to use effective contraception from the screening period until at least 6 months after drug product infusion. Male subjects are also required to use effective contraception (including condoms) from the screening period until at least 6 months after drug product infusion.
• Live vaccines were administered within 6 weeks prior to screening.
• Known history of hypersensitivity to the ingredients used in the trial.
• An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol.