Transfusion Dependent Beta-ThalassemiaEarly Phase 1NCT05762510
A Study Evaluating the Safety and Efficacy of LentiRed Drug Product in Transfusion-dependent β-Thalassemia [TDT]
A Early Phase 1 study testing GMCN-508B (LentiRed) in people with Transfusion Dependent Beta-Thalassemia, run by First Affiliated Hospital of Guangxi Medical University at 1 site in China.
Trial summary
This is a single-arm, open label, single-dose study in subjects with transfusion dependent β-thalassaemia. The study will evaluate the safety and efficacy of autologous CD34+ Human Hematopoietic Stem Cells that was transduced with LentiRed Lentivrial vector. Read more about this study
- Who is it for?
- Ages 5 to 35 years
- Conditions the study is for
- Transfusion Dependent Beta-Thalassemia
- What is being tested?
- GMCN-508B (LentiRed)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 22 Feb 2023to 31 Oct 2030
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The affiliated hospital of guangxi medical university
Nanning, Guangxi, 530021
yongrong lai, PhD, 86-771-5356746, laiyongrong@hotmail.com
yongrong lai, PhD
About this study
Official title: An Open Label Study Evaluating the Safety and Efficacy of Gene Therapy for Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a LentiRed Lentiviral Vector (GMCN-508B Drug Product, Also Called LentiRed)
This is a single-arm, open label, single-dose study in subjects with transfusion dependent β-thalassaemia. The study will evaluate the safety and efficacy of autologous CD34+ Human Hematopoietic Stem Cells that was transduced with LentiRed Lentivrial vector.
Read the detailed description
Subject participation for this study will be 5 years.
- Conditions
- Transfusion Dependent Beta-Thalassemia
- Being tested
- GMCN-508B (LentiRed)
- Keywords
- LentiRed, Beta-Thalassemia, Human Hematopoietic Stem Cell, gene therapy, CD34+
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GMCN-508B (LentiRed)Genetic
LentiRed Drug Product is administered by intravenous infusion following myeloablative conditioning with busulfan.
| Study group | Role | What they receive |
|---|---|---|
| LentiRed | Experimental | LentiRed Drug Product Receives: Genetic: GMCN-508B (LentiRed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects who achieved transfusion independence, defined as an average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 6 months at any time during the study after LentiRed Drug Product infusion.
TI was defined as an average hemoglobin (Hb) >= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of >=6 months at any time during the study after Drug Product infusion.
Measured: From time of drug product infusion up to 24 months
Number and proportion of subjects who maintained βA-T87Q-globin(HbAT87Q) at ≥2.0 g/dL for ≥ 6 months after LentiRed Drug Product infusion.
Percentage of participants with sustained production of >=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months was reported.
Measured: From time of drug product infusion up to 24 months
Proportion of subjects whose red blood cells (RBC) transfusion requirement was reduced for ≥6 months after LentiRed Drug Product infusion, compared to previous 2-year transfusion records.
The annualized number of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized number of pRBC transfusions post drug product infusion and the percentage change was reported.
Measured: From time of drug product infusion up to 24 months
Secondary outcomes (9)
Proportion of subjects who achieved transfusion independence, defined as an average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 3 months at any time during the study after LentiRed Drug Product infusion.
TI was defined as an average hemoglobin (Hb) >= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of >=3 months at any time during the study after Drug Product infusion.
Measured: From time of drug product infusion up to 24 months
Proportion of subjects who achieved 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.
Measured: From time of drug product infusion up to 24 months
Incidence of transplant-related mortality through 100 days post drug product infusion.
Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant.)
Measured: Through 100 days post-Drug Product infusion
Overall survival.
Overall survival was defined as time from date of LentiRed Drug Product infusion (Day 0) to date of death.
Measured: From time of drug product infusion up to 24 months
Detection of vector-derived replication competent lentivirus (RCL) in any subject.
Blood samples were analyzed for detection of RCL
Measured: From time of drug product infusion up to 24 months
Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia.
Linear amplification-mediated polymerase chain reaction (LAM-PCR) coupled with next generation sequencing and subsequent (semi-) automated data mining allowed high-throughput analysis of vector integration site (IS) in blood cells from treated participants at multiple time points. ISs detected in peripheral blood cells at early time points generally were due to the expansion of transduced short-term progenitor stem cell clones, and gradually shift to include sites detected due to expansion of transduced long-term stem cell clones. An efficient transduction procedure was anticipated to give rise to a polyclonal population in the participant, reflected by the detection of multiple IS. Additionally, ISA allowed monitoring of the relative contribution of individual clones over time. Number of participants who had IS that contributed to >=30% of the total clones at any time was used as a first step to investigating whether clonal dominance was achieved.
Measured: From time of drug product infusion up to 24 months
Monitor of frequency of clinical adverse events (AEs).
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.
Measured: From signing of informed consent to 24 months after the drug product infusion
Therapeutic globin expression, as measured by assessing the ratio of βA-T87Q-globin to α -globin in whole blood, as well as the amount of βA-T87Q-globin to as a fraction of all β -chains in whole blood.
globin expression measured by HPLC
Measured: From time of drug product infusion up to 24 months
Average vector copy number (VCN) in cell populations from peripheral blood and bone marrow containing the integrated LentiRed lentiviral vector.
VCN will be monitored after drug product transfusion
Measured: From time of drug product infusion up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2023
- Study start22 Feb 2023
- Primary completion1 Apr 2028 (estimated)
- Study completion31 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transfusion Dependent Beta-ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Guangxi Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Genmedicn Biopharma Ltd.
- Responsible party
- Principal investigator, Yongrong Lai, First Affiliated Hospital of Guangxi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05762510
- Sponsor's protocol ID
- 2021-1101-001
- Status last verified
- May 2023
- First submitted
- 6 Jan 2022
- Last updated
- 9 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study Evaluating the Safety and Efficacy of Gene Therapy for Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a LentiRed Lentiviral Vector (GMCN-508B Drug Product, Also Called LentiRed)
- ClinicalTrials.gov ID
- NCT05762510
- Acronym / sponsor ID
- 2021-1101-001
- Conditions
- Transfusion Dependent Beta-Thalassemia
- Keywords
- LentiRed, Beta-Thalassemia, Human Hematopoietic Stem Cell, gene therapy, CD34+
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Guangxi Medical UniversityUniversity, hospital or other
- Collaborators
- Genmedicn Biopharma Ltd.
- Study start
- 22 Feb 2023 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 31 Oct 2030 (estimated)
- First posted
- 9 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, open label, single-dose study in subjects with transfusion dependent β-thalassaemia. The study will evaluate the safety and efficacy of autologous CD34+ Human Hematopoietic Stem Cells that was transduced with LentiRed Lentivrial vector.
Detailed description
Subject participation for this study will be 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LentiRed | Experimental | Genetic: GMCN-508B (LentiRed)LentiRed Drug Product |
Who may qualify
- Ages
- 5 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (23 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GMCN-508B (LentiRed)LentiRed Drug Product is administered by intravenous infusion following myeloablative conditioning with busulfan. | Genetic | LentiRed |
Primary outcome
Proportion of subjects who achieved transfusion independence, defined as an average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 6 months at any time during the study after LentiRed Drug Product infusion.
Time frame: From time of drug product infusion up to 24 months
TI was defined as an average hemoglobin (Hb) >= 9 g/dL without any packed red blood cells (pRBC) transfusions for a continuous period of >=6 months at any time during the study after Drug Product infusion.
Number and proportion of subjects who maintained βA-T87Q-globin(HbAT87Q) at ≥2.0 g/dL for ≥ 6 months after LentiRed Drug Product infusion.
Time frame: From time of drug product infusion up to 24 months
Percentage of participants with sustained production of >=2.0 grams per deciliter (g/dL) of hemoglobin A (HbA) containing βA-T87Q-globin (HbAT87Q) for 6 months was reported.
Proportion of subjects whose red blood cells (RBC) transfusion requirement was reduced for ≥6 months after LentiRed Drug Product infusion, compared to previous 2-year transfusion records.
Time frame: From time of drug product infusion up to 24 months
The annualized number of pRBC transfusions over the 2 year period prior to drug product infusion was compared to the annualized number of pRBC transfusions post drug product infusion and the percentage change was reported.
9 secondary outcomes
Proportion of subjects who achieved transfusion independence, defined as an average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 3 months at any time during the study after LentiRed Drug Product infusion.
Time frame: From time of drug product infusion up to 24 months
Proportion of subjects who achieved Neutrophil engraftment.
Time frame: From time of drug product infusion up to 24 months
Incidence of transplant-related mortality through 100 days post drug product infusion.
Time frame: Through 100 days post-Drug Product infusion
Overall survival.
Time frame: From time of drug product infusion up to 24 months
Detection of vector-derived replication competent lentivirus (RCL) in any subject.
Time frame: From time of drug product infusion up to 24 months
Characterization of events of insertional mutagenesis leading to clonal dominance or leukemia.
Time frame: From time of drug product infusion up to 24 months
Monitor of frequency of clinical adverse events (AEs).
Time frame: From signing of informed consent to 24 months after the drug product infusion
Therapeutic globin expression, as measured by assessing the ratio of βA-T87Q-globin to α -globin in whole blood, as well as the amount of βA-T87Q-globin to as a fraction of all β -chains in whole blood.
Time frame: From time of drug product infusion up to 24 months
Average vector copy number (VCN) in cell populations from peripheral blood and bone marrow containing the integrated LentiRed lentiviral vector.
Time frame: From time of drug product infusion up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing GMCN-508B (LentiRed) in people with Transfusion Dependent Beta-Thalassemia, run by First Affiliated Hospital of Guangxi Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yongrong Lai, PhD (86-771-5356746, laiyongrong@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects who achieved transfusion independence, defined as an average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 6 months at any time during the study after LentiRed Drug Product infusion. (time frame: From time of drug product infusion up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.