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)

First Affiliated Hospital of Guangxi Medical University1 site in 1 country5 target enrollmentMay 8, 2023

ConditionsTransfusion-dependent α-Thalassemia

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Transfusion-dependent α-Thalassemia
Sponsor: First Affiliated Hospital of Guangxi Medical University
Enrollment: 5
Locations: 1
Primary Endpoint: Percentage of Participants Who Achieved Transfusion Independence (TI)
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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].

Detailed Description

Subject participation for this study will be 5 years.

Registry

clinicaltrials.gov

Start Date

May 8, 2023

End Date

December 31, 2030

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

First Affiliated Hospital of Guangxi Medical University

Responsible Party

Principal Investigator

Yongrong Lai

MD, Director of Hematology Department of First Affiliated Hospital of Guangxi Medical University

First Affiliated Hospital of Guangxi Medical University

Eligibility Criteria

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 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.
•Karnofsky Level of Performance (KPS) score or Lansky Level of Performance (LPS) score ≥
•Subjects were determined to undergo autologous hematopoietic stem cell transplantation and conditioning procedure by the principle investigator.
•Subjects were willing to comply with the protocol.
•Fertile Subjects are willing to take effective contraceptive measures during the study.

Exclusion Criteria

•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.
•Uncorreted Bleeding disorders with frequent bleeding (eg, menorrhagia, epistaxis, coagulation disorders).
•Bacterial, fungal, parasitic or viral infection as determined by the investigator to be clinically significant.
•Presence of severe iron overload.
•Any prior or current malignancy, myeloproliferative disorders or immunodeficiency disorders.
•Any major medical disease, laboratory test abnormality or mental illness that would render the participant ineligible for the study.
•Immediate family member with a known Familial Cancer Syndrome.
•Prior receipt of gene therapy, allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation.
•Participation in another clinical study with an investigational drug 3 months prior to Screening.
•Pregnancy, plan to be pregnant during study or breastfeeding in a postpartum female.

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved Transfusion Independence (TI)

Time Frame: From time of drug product infusion up to 24 months

TI was defined as a weighted average hemoglobin (Hb) \>= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of \>=12 months at any time during the study after GMCN-508A Drug Product infusion. Percentage of participants who achieved TI from time of drug product infusion up to 24 months was reported.

Secondary Outcomes

Annualized Number of pRBC Transfusions(From 12 to 24 months post drug product infusion)
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)(From time of drug product infusion up to 24 months)
Change From Baseline in Serum Ferritin(Baseline, Month 12 and 24)
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 24(Month 24)
Duration of Transfusion Independence (TI)(From time of drug product infusion up to 24 months)
Time From GMCN-508A Drug Product Infusion to Achieving Transfusion Independence (TI)(From time of drug product infusion up to 24 months)
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score(Baseline, Month 12 and 24)
Proportion of Participants With Successful Neutrophil Engraftment(From time of drug product infusion up to 24 months)
Overall Survival(From time of drug product infusion up to 24 months)
Incidence of acute and/or chronic graft-versus-host disease (GVHD)(From time of drug product infusion up to 24 months)
Percentage of Participants with occurrence of malignant disease(From time of drug product infusion up to 24 months)
Annualized Volume of pRBC Transfusions(From 12 to 24 months post drug product infusion)
Change From Baseline in Cardiac T2* on MRI(Baseline, Month 12 and 24)
Proportion of Participants With Successful Platelet Engraftment(From time of drug product infusion up to 24 months)
Change From Baseline in Short Form-36 Health Survey (SF-36)(Baseline, Month 12 and 24)
Proportions of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From signing of informed consent to 24 months after the drug product infusion)
Proportion of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion.(From 6 to 24 months)
Time to Neutrophil Engraftment(From time of drug product infusion up to 24 months)
Time to Platelet Engraftment(From time of drug product infusion up to 24 months)
Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI)(Baseline, Month 12 and 24)
Transplant-related Mortality(Through 100 and 365 days post GMCN-508A Drug Product infusion)
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)(From time of drug product infusion up to 24 months)