Clinical trial NCT05757245: A Study Evaluating the Safety and Efficacy of the GMCN-508A Drug Product in Transfusion-dependent α-Thalassemia Participants
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Transfusion-dependent α-Thalassemia
Keywords: GMCN-508A
gene therapy
Transfusion-dependent α-Thalassemia
Human Hematopoietic Stem Cell
Lead sponsor: First Affiliated Hospital of Guangxi Medical University
Sponsor class: OTHER
Collaborators: name: Genmedicn Biopharma Ltd.
First posted: 2023-03-07
Enrollment: 5
Sex: ALL
Minimum age (years): 5
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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