A Study Evaluating the Safety and Efficacy of the GMCN-508A Drug Product in Transfusion-dependent α-Thalassemia Participants

A Phase 1 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With Transfusion-dependent α-Thalassemia by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral Vector (GMCN-508A Drug Product)

This is a non-randomized, open label, single-site, single-dose, phase 1 study in up to 5 participants (between 5 and 35 years of age, inclusive) with Transfusion-dependent α-thalassemia. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using GMCN-508A Drug Product [autologous CD34+ hematopoietic stem cells transduced with GMCN-508A lentiviral vector encoding the human α-globin gene].

Subject participation for this study will be 5 years.

Inclusion Criteria:

1. 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.
2. Ages 5 to 35, no gender limitation.
3. The clinical diagnosis of Transfusion-dependent α-Thalassemia.Transfusion dependence was defined as ≥6 Units of transfusions of pRBCs for the prior 24 weeks without >56 days of non-transfusion.
4. Karnofsky Level of Performance (KPS) score or Lansky Level of Performance (LPS) score ≥70.
5. Subjects were determined to undergo autologous hematopoietic stem cell transplantation and conditioning procedure by the principle investigator.
6. Subjects were willing to comply with the protocol.
7. Fertile Subjects are willing to take effective contraceptive measures during the study.

Exclusion Criteria:

1. Diagnosed with mild α-thalassemia, Hb Bart's edema, ATRx α-thalassemia, hemoglobin S/β-thalassemia, myelodysplastic subtype anemia, or with HbE homozygous β gene mutation, or with any type of β-thalassemia Thalassemia.
2. Uncorreted Bleeding disorders with frequent bleeding (eg, menorrhagia, epistaxis, coagulation disorders).
3. Bacterial, fungal, parasitic or viral infection as determined by the investigator to be clinically significant.
4. Presence of severe iron overload.
5. Any prior or current malignancy, myeloproliferative disorders or immunodeficiency disorders.
6. Any major medical disease, laboratory test abnormality or mental illness that would render the participant ineligible for the study.
7. Immediate family member with a known Familial Cancer Syndrome.
8. Prior receipt of gene therapy, allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation.
9. Participation in another clinical study with an investigational drug 3 months prior to Screening.
10. Pregnancy, plan to be pregnant during study or breastfeeding in a postpartum female.
11. Known hypersensitivity to any ingredients or excipients of the test drug.
12. Eligible for allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation with a known and available donor.
13. Any other condition that would render the participant ineligible for the study, as determined by the investigator.