Back to resultsA Study Evaluating the Safety and Efficacy of the GMCN-508A Drug Product in Transfusion-dependent α-Thalassemia Participants
Primary Purpose
Transfusion-dependent α-Thalassemia
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
GMCN-508A Drug Product
Sponsored by
About this trial
This is an interventional treatment trial for Transfusion-dependent α-Thalassemia focused on measuring GMCN-508A, gene therapy, Transfusion-dependent α-Thalassemia, Human Hematopoietic Stem Cell
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 ≥70. 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. Known hypersensitivity to any ingredients or excipients of the test drug. Eligible for allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation with a known and available donor. Any other condition that would render the participant ineligible for the study, as determined by the investigator.
Sites / Locations
- The affiliated hospital of guangxi medical universityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GMCN-508A
Arm Description
GMCN-508A infusion
Outcomes
Primary Outcome Measures
Percentage of Participants Who Achieved Transfusion Independence (TI)
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 Outcome Measures
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 24
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion.
Duration of Transfusion Independence (TI)
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion. Time period of TI will start when participants achieve a Hb >= 9 g/dL with no transfusions in the preceding 60 days. Duration of TI was calculated as the time from the start of TI (i.e. first Hb >= 9 g/dL with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met.
Time From GMCN-508A Drug Product Infusion to Achieving Transfusion Independence (TI)
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion. Time from drug product infusion to initial achievement of TI was calculated as the time from drug product infusion to the first Hb at which a participant can be declared as TI.
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)
The weighted average Hb is an average area under the curve during the period of TI, from the start of TI when the Hb is first >= 9 g/dL with no transfusions in the preceding 60 days to the last available Hb at which the TI criteria are still met.
Annualized Number of pRBC Transfusions
Annualized number of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized number of transfusions during the 24 months prior to enrollment.
Annualized Volume of pRBC Transfusions
Annualized volume of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized volume of transfusions during the 24 months prior to enrollment.
Proportion of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion.
Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI)
Change From Baseline in Cardiac T2* on MRI
Change From Baseline in Serum Ferritin
Time to Neutrophil Engraftment
Time to neutrophil engraftment was defined as the time to the first of 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L obtained on different days after a post-transplant value of < 0.5 × 10^9/L. The Day of neutrophil engraftment is the first day of the 3 consecutive measurements, where Day 0 is the day of drug product infusion.
Proportion of Participants With Successful Platelet Engraftment
Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Time to Platelet Engraftment
Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score
PedsQL GCS is designed to measure health-related quality of life in pediatric participants and adolescents (2 to 18 years of age). It encompasses 4 dimensions of functioning (physical [8 items], emotional [5 items], social [5 items], school [3 items]). Age groups: Toddler (2-4 years), Young pediatric (5-7 years), Pediatric (8-12 years), and Teens (13-18 years). Depending on the participant's age, the questionnaire may be completed by parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consist of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consist of 23 items, with a 3-point Likert scale (0, 2, 4) for the young pediatric, and a 5-point Likert scale for the pediatric and teens groups. Scores are transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate improved quality of life.
Change From Baseline in Short Form-36 Health Survey (SF-36)
SF-36 is a generic quality-of-life instrument that had been widely used to assess HRQL of participants. Generic instruments were used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning [1=yes, limited a lot to 3=no, not limited at all], role-physical [1=all of the time to 5=none of the time], bodily pain [1=very severe to 6=none], general health [1=poor to 5=excellent], vitality [1=none of the time to 5=all of the time], social functioning [1=all of the time: to 5=none of the time], role emotional [1=all of the time to 5=none of the time] and mental health [1=all of the time to 5=none of the time]), with scores ranged from 0 to 100. Higher scores indicating better HRQL.
Proportion of Participants With Successful Neutrophil Engraftment
Neutrophil engraftment was defined as achieving 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L on different days after a post-transplant value of < 0.5 × 10^9/L within 42 days after drug product infusion.
Transplant-related Mortality
Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)
Proportions of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE, occurring at any dose and regardless of causality that: results in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect.
Overall Survival
Overall survival was defined as time from date of GMCN-508A Drug Product infusion (Day 0) to date of death. Overall survival was censored at the date of last visit if the participant was still alive. Percentage of participants who survived throughout the study were reported.
Incidence of acute and/or chronic graft-versus-host disease (GVHD)
acute and/or chronic graft-versus-host disease (GVHD) was determined by the investigator.
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)
Percentage of Participants with occurrence of malignant disease
Full Information
NCT ID
NCT05757245
First Posted
February 24, 2023
Last Updated
April 16, 2023
Sponsor
First Affiliated Hospital of Guangxi Medical University
Collaborators
Genmedicn Biopharma Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05757245
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2023 (Anticipated)
Primary Completion Date
August 1, 2028 (Anticipated)
Study Completion Date
December 31, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
First Affiliated Hospital of Guangxi Medical University
Collaborators
Genmedicn Biopharma Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transfusion-dependent α-Thalassemia
Keywords
GMCN-508A, gene therapy, Transfusion-dependent α-Thalassemia, Human Hematopoietic Stem Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GMCN-508A
Arm Type
Experimental
Arm Description
GMCN-508A infusion
Intervention Type
Genetic
Intervention Name(s)
GMCN-508A Drug Product
Intervention Description
Transplant of autologous hematopoietic stem and progenitor cells transduced with GMCN-508A lentiviral vector.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Transfusion Independence (TI)
Description
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.
Time Frame
From time of drug product infusion up to 24 months
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 24
Description
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion.
Time Frame
Month 24
Title
Duration of Transfusion Independence (TI)
Description
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion. Time period of TI will start when participants achieve a Hb >= 9 g/dL with no transfusions in the preceding 60 days. Duration of TI was calculated as the time from the start of TI (i.e. first Hb >= 9 g/dL with no transfusions in the preceding 60 days) up to the last available Hb at which the TI criteria are still met.
Time Frame
From time of drug product infusion up to 24 months
Title
Time From GMCN-508A Drug Product Infusion to Achieving Transfusion Independence (TI)
Description
TI was defined as a weighted average Hb >= 9 g/dL without any pRBC transfusions for a continuous period of >= 12 months at any time during the study after GMCN-508A Drug Product infusion. Time from drug product infusion to initial achievement of TI was calculated as the time from drug product infusion to the first Hb at which a participant can be declared as TI.
Time Frame
From time of drug product infusion up to 24 months
Title
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)
Description
The weighted average Hb is an average area under the curve during the period of TI, from the start of TI when the Hb is first >= 9 g/dL with no transfusions in the preceding 60 days to the last available Hb at which the TI criteria are still met.
Time Frame
From time of drug product infusion up to 24 months
Title
Annualized Number of pRBC Transfusions
Description
Annualized number of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized number of transfusions during the 24 months prior to enrollment.
Time Frame
From 12 to 24 months post drug product infusion
Title
Annualized Volume of pRBC Transfusions
Description
Annualized volume of pRBC transfusions from 12 months post-drug product infusion through Month 24 compared to the annualized volume of transfusions during the 24 months prior to enrollment.
Time Frame
From 12 to 24 months post drug product infusion
Title
Proportion of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion.
Time Frame
From 6 to 24 months
Title
Change From Baseline in liver Iron Content by Magnetic Resonance Imaging (MRI)
Time Frame
Baseline, Month 12 and 24
Title
Change From Baseline in Cardiac T2* on MRI
Time Frame
Baseline, Month 12 and 24
Title
Change From Baseline in Serum Ferritin
Time Frame
Baseline, Month 12 and 24
Title
Time to Neutrophil Engraftment
Description
Time to neutrophil engraftment was defined as the time to the first of 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L obtained on different days after a post-transplant value of < 0.5 × 10^9/L. The Day of neutrophil engraftment is the first day of the 3 consecutive measurements, where Day 0 is the day of drug product infusion.
Time Frame
From time of drug product infusion up to 24 months
Title
Proportion of Participants With Successful Platelet Engraftment
Description
Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Time Frame
From time of drug product infusion up to 24 months
Title
Time to Platelet Engraftment
Description
Platelet engraftment was defined as achieving 3 consecutive platelet values >= 20 × 10^9/L on different days after a post-transplant value of < 20 × 10^9/L, while no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
Time Frame
From time of drug product infusion up to 24 months
Title
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale (GCS) Score
Description
PedsQL GCS is designed to measure health-related quality of life in pediatric participants and adolescents (2 to 18 years of age). It encompasses 4 dimensions of functioning (physical [8 items], emotional [5 items], social [5 items], school [3 items]). Age groups: Toddler (2-4 years), Young pediatric (5-7 years), Pediatric (8-12 years), and Teens (13-18 years). Depending on the participant's age, the questionnaire may be completed by parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consist of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL GCS consist of 23 items, with a 3-point Likert scale (0, 2, 4) for the young pediatric, and a 5-point Likert scale for the pediatric and teens groups. Scores are transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate improved quality of life.
Time Frame
Baseline, Month 12 and 24
Title
Change From Baseline in Short Form-36 Health Survey (SF-36)
Description
SF-36 is a generic quality-of-life instrument that had been widely used to assess HRQL of participants. Generic instruments were used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consisted of 36 items that were aggregated into 8 multi-item scales (physical functioning [1=yes, limited a lot to 3=no, not limited at all], role-physical [1=all of the time to 5=none of the time], bodily pain [1=very severe to 6=none], general health [1=poor to 5=excellent], vitality [1=none of the time to 5=all of the time], social functioning [1=all of the time: to 5=none of the time], role emotional [1=all of the time to 5=none of the time] and mental health [1=all of the time to 5=none of the time]), with scores ranged from 0 to 100. Higher scores indicating better HRQL.
Time Frame
Baseline, Month 12 and 24
Title
Proportion of Participants With Successful Neutrophil Engraftment
Description
Neutrophil engraftment was defined as achieving 3 consecutive absolute neutrophil count (ANC) >= 0.5 × 10^9/L on different days after a post-transplant value of < 0.5 × 10^9/L within 42 days after drug product infusion.
Time Frame
From time of drug product infusion up to 24 months
Title
Transplant-related Mortality
Description
Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)
Time Frame
Through 100 and 365 days post GMCN-508A Drug Product infusion
Title
Proportions of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE, occurring at any dose and regardless of causality that: results in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect.
Time Frame
From signing of informed consent to 24 months after the drug product infusion
Title
Overall Survival
Description
Overall survival was defined as time from date of GMCN-508A Drug Product infusion (Day 0) to date of death. Overall survival was censored at the date of last visit if the participant was still alive. Percentage of participants who survived throughout the study were reported.
Time Frame
From time of drug product infusion up to 24 months
Title
Incidence of acute and/or chronic graft-versus-host disease (GVHD)
Description
acute and/or chronic graft-versus-host disease (GVHD) was determined by the investigator.
Time Frame
From time of drug product infusion up to 24 months
Title
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)
Time Frame
From time of drug product infusion up to 24 months
Title
Percentage of Participants with occurrence of malignant disease
Time Frame
From time of drug product infusion up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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 ≥70.
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.
Known hypersensitivity to any ingredients or excipients of the test drug.
Eligible for allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation with a known and available donor.
Any other condition that would render the participant ineligible for the study, as determined by the investigator.
Facility Information:
Facility Name
The affiliated hospital of guangxi medical university
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
yongrong lai, PhD
Phone
86-771-5356746
Email
laiyongrong@hotmail.com
First Name & Middle Initial & Last Name & Degree
yongrong lai, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study Evaluating the Safety and Efficacy of the GMCN-508A Drug Product in Transfusion-dependent α-Thalassemia Participants
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