Β-thalassemiaPhase 1NCT06655662
Evaluating Safety and Efficacy of Lentiviral-transduced CD34+ HSCs in Β-thalassaemia Patients.
A Phase 1 study testing β-globin restored autologous hematopoietic stem cells in people with Β-thalassemia, run by Shenzhen Hemogen at 3 sites in China.
Trial summary
This is a single-arm, open label, multi-center, single-dose Phase 1 clinical trial in subjects with transfusion dependent β-thalassaemia. The study aims to evaluate the safety and efficacy of autologous lentiviral-transduced CD34+ human hematopoietic stem cells (hHSCs) using the gene therapy product HGI-001. Read more about this study
- Who is it for?
- Ages 6 to 35 years
- Conditions the study is for
- Β-thalassemia
- What is being tested?
- β-globin restored autologous hematopoietic stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesChina
- Study dates
- 12 Jun 2024to 31 Dec 2026
- Phase
- 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 6 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Aged 6-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
- Definitively diagnosed with severe TDT without genotype restriction (excluding patients with coexisting α-thalassemia), and a valid test report can be provided;
- Average transfusion volume > 100 mL/kg/year or transfusion frequency > 8 times/year within 2 years prior to enrollment；
- At least 3 months of full volume transfusion (verification of blood transfusion records can be provided) prior to screening, and Hb is maintained at ≥ 9.0 g/dL;
- Serum ferritin level less than 5000μg/L, with moderate or lower iron overload in the heart and liver as indicated by magnetic resonance imaging (MRI T2*), specifically liver MRI T2* greater than 1.4ms and cardiac MRI T2* greater than 10ms;
- Acceptable organ functions (including heart, liver, kidney, lung and coagulation functions), stable disease condition, and suitable for busulfan pre-treatment and hematopoietic stem cell (HSC) transplantation as judged by the investigator;
- Meets follow-up requirements, adheres to treatment arrangements, and is able to return to the hospital regularly to undergo various examinations within 2 years after reinfusion of HGI-001 injection.
Who cannot join
- Patients with fully HLA-matched donors;
- Having previously received gene therapy, gene editing therapy, or allogeneic hematopoietic stem cell transplantation;
- Uncorrected bleeding disorder;
- Uncontrolled epilepsy and mental illness;
- Within the past 3 months prior to enrollment, the use of Luspatercept, Hydroxyurea, Ruxolitinib, Thalidomide, Decitabine, or Ara-c has been administered；
- Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
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- Patients with pulmonary hypertension who have not been given effective intervention;
- Positive for anti-RBC antibodies in antibody screening;
- Hepatitis B surface antigen (HBsAg) is positive and the HBV DNA copy number is greater than the upper limit of the normal value of the detection unit (those who are negative do not need to test for HBV DNA copy number), antibodies to Hepatitis C virus (HCV) are positive, antibodies to Human Immunodeficiency Virus (HIV) are positive, or antibodies to Treponema pallidum (TP-Ab) are positive (subjects who are positive due to vaccination are eligible for enrollment). Additionally, the results of Hepatitis B Virus (HBV) DNA testing, Hepatitis C Virus (HCV) RNA testing, Cytomegalovirus DNA testing, and Epstein-Barr Virus (EBV) DNA testing are abnormal；
- Have or have had malignant tumors or myeloproliferative diseases or immunodeficiency disorders or autoimmune diseases;
- Have a first-degree relative with a history of or suspected hereditary cancer (including but not limited to hereditary breast and ovarian cancer, nonpolyposis colorectal cancer, and adenomatous polyposis);
- Severe bacterial, viral, fungal or parasitic infection;
- Other illnesses which render the subject unsuitable for participation (e.g., severe liver, kidney or heart disease); Definition of severe liver and kidney disease: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin > 3 × ULN; b. Liver magnetic resonance imaging (MRI) indicates significant cirrhosis; c. Liver biopsy indicates cirrhosis, severe fibrosis or active hepatitis (liver biopsy is only performed when liver MRI indicates active hepatitis and significant fibrosis without evidence for cirrhosis); d. Creatinine clearance <60 mL/(min·1.73m^2);
- WBC < 3 × 10^9/L and/or PLT < 100 × 10^9/L;
- Has diabetes, abnormal thyroid functions or other endocrine disorder;
- Participated in other interventional clinical studies within 4 weeks before the trial;
- Poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Guangxi Medical University First Affiliated Hospital
Guangxi
Haigang Sun, 13823168465, sunhaigang@genomics.cn
Linxia Qian, 18851685852, qianlinxia@genomics.cn
- Recruiting
Shenzhen Children's Hospital
Shenzhen
- Recruiting
Shenzhen University General Hospital
Shenzhen
About this study
Official title: An Open, Multi-center, Phase I Clinical Study on the Safety and Efficacy of HGI-001 Injection in Patients with Transfusion-Dependent Β-Thalassemia.
This is a single-arm, open label, multi-center, single-dose Phase 1 clinical trial in subjects with transfusion dependent β-thalassaemia. The study aims to evaluate the safety and efficacy of autologous lentiviral-transduced CD34+ human hematopoietic stem cells (hHSCs) using the gene therapy product HGI-001.
Read the detailed description
The investigators will recruit transfusion-dependent β-thalassaemia patients and collect their autologous hematopoietic stem cells, which will be modified with the LentiHBBT87Q system to restore β-globin expression. After conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.
- Conditions
- Β-thalassemia
- Being tested
- β-globin restored autologous hematopoietic stem cells
- Keywords
- β-thalassemia, Thalassemia, Genetic Diseases, Inborn, Hemoglobinopathies, Hematologic Diseases, Anemia, Anemia, Hemolytic, Anemia, Hemolytic, Congenital
- Medical subject headings
- Thalassemia, Genetic Diseases, Inborn, Hemoglobinopathies, Hematologic Diseases, Anemia, Anemia, Hemolytic, Anemia, Hemolytic, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
β-globin restored autologous hematopoietic stem cellsOther
Eight transfusion-dependent β-thalassaemia subjects aged 6-35 years will be reinfused with β-globin restored autologous hematopoietic stem cells modified with LentiHBBT87Q
| Study group | Role | What they receive |
|---|---|---|
| β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q | Experimental | This arm involves the transduction of autologous hematopoietic stem cells with a lentiviral vector carrying the β-globin gene modified with LentiHBBT87Q. Subjects aged 6-35 years with transfusion-dependent β-thalassaemia will receive a infusion of these modified stem cells. Receives: Other: β-globin restored autologous hematopoietic stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transfusion Independence (TI) Rate
Percent of subjects who achieve transfusion independence, defined as not requiring transfusion for at least 12 consecutive months post-HGI-001 injection, with a weighted average Hb of ≥ 9.0 g/dL. Calculated from the point hemoglobin reaches ≥9 g/dL and no transfusions have occurred in the last 60 days.
Measured: 0-24 Months
Incidence and Severity of Adverse Events (AEs) Related to Transplantation
Number and percentage of adverse events related to transplantation, summarized according to NCI CTCAE 5.0.
Measured: 0-24 Months
Incidence of Serious Adverse Events (SAEs) Related to Transplantation
Number of serious adverse events related to transplantation, summarized according to NCI CTCAE 5.0.
Measured: 0-24 Months
Overall Survival Rate During the Clinical Trial
Number of patients alive throughout the entire trial period.
Measured: 0-24 Months
Percentage of Negative Replicating Lentivirus Test Post-HGI-001 Injection
The percentage of participants with negative results for replicating lentivirus in the 24 months following HGI-001 injection.
Measured: 0-24 Months
Number of Participants with Normal Clonal Variations Post-Transplant
Evaluation of the percentage of participants who do not exhibit abnormal clonal proliferation and maintain polyclonal engraftment following transplantation.
Measured: 0-24 Months
Number of Participants Experiencing Transplantation-related Fatal and Disabling Events Within 100 Days Post-transplantation
The number of participants who experience transplantation-related fatal and disabling events within 100 days after transplantation will be recorded and summarized.
Measured: 0-100Days
Number of Patients with Abnormal Hematology and Bone Marrow Cytology Post-Reinfusion
Number of patients exhibiting abnormal hematology and bone marrow cytology findings within 24 months after reinfusion, and the percentage of patients with abnormal RBC proliferation.
Measured: 0-24 Months
Secondary outcomes (9)
Percentage of Subjects Achieving Transfusion Cessation for Over 6 Months Post-HGI-001 Injection
Percent of subjects who do not require transfusion for at least 6 consecutive months after reinfusion of HGI-001 injection
Measured: 0-24 Months
Percentage of Subjects with Successful HSC Engraftment
Percentage of subjects meeting criteria for successful engraftment, defined as an absolute neutrophil count > 0.5 × 10^9/L for 3 consecutive days and a platelet count maintained at > 20 × 10^9/L for 7 consecutive days without platelet transfusion.
Measured: 1 month
Percentage Change in Annual Transfusion Volume or Frequency
Percentage change in average annual transfusion volume or frequency from baseline.
Measured: 0-24 Months
Transfusion Improvement Rate
Percentage of subjects with a decrease of 30% or more in the average annual transfusion volume or frequency (0-12 months, 12-24 months) from baseline after reinfusion of HGI-001 injection.
Measured: 0-24 Months
Change in Vector Copy Number (VCN) Post-Transplantation
The change in vector copy number (VCN) from the baseline measurement at the time of transplantation to 24 months post-transplantation, as assessed by quantitative PCR.
Measured: 0-24 Months
Change in Exogenous Adult Hemoglobin HbAT87Q Expression Levels Post-Transplantation
The change in expression levels of exogenous adult hemoglobin HbAT87Q from baseline to 24 months post-transplantation, calculated using high-performance liquid chromatography (HPLC) in conjunction with the ratio of HbA to total hemoglobin.
Measured: 0-24 Months
Changes in Cardiac and Liver Iron Load Post-HGI-001 Infusion
Assessment of the changes in cardiac and liver iron load as measured by MRI T2* imaging following the reinfusion of HGI-001 injection.
Measured: 0-24 Months
Time to and Duration of Transfusion Independence in Subjects Post-HGI-001 Infusion
Time from Day 0 to achievement of transfusion independence (TI) and the duration of maintaining TI; average total hemoglobin (Hb) and HbAT87Q levels during the TI period.
Measured: 0-24 Months
Change in Serum Ferritin Levels Post-HGI-001 Infusion
The change in serum ferritin levels following the reinfusion of HGI-001 injection.
Measured: 0-24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2024
- Study start12 Jun 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Β-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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This phase 1 study employs a single-group, open-label design to evaluate the safety and preliminary efficacy of a gene therapy product. It is anticipated that 8 participants will be enrolled to receive a single administration of the investigational gene therapy. The primary focus will be on monitoring participants for adverse events and assessing the product's safety profile and potential therapeutic benefits.
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen Hemogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chao Liu, PHD, Principal investigator, Shenzhen HemogenSixi Liu, Professor, Principal investigator, Shenzhen Children's HospitalYongrong Lai, Professor, Principal investigator, First Affiliated Hospital of Guangxi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06655662
- Sponsor's protocol ID
- HGI-001C04
- Status last verified
- Oct 2024
- First submitted
- 18 Oct 2024
- Last updated
- 23 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Multi-center, Phase I Clinical Study on the Safety and Efficacy of HGI-001 Injection in Patients with Transfusion-Dependent Β-Thalassemia.
- ClinicalTrials.gov ID
- NCT06655662
- Acronym / sponsor ID
- HGI-001C04
- Conditions
- Β-thalassemia
- Keywords
- β-thalassemia, Thalassemia, Genetic Diseases, Inborn, Hemoglobinopathies, Hematologic Diseases, Anemia, Anemia, Hemolytic, Anemia, Hemolytic, Congenital
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- Shenzhen HemogenIndustry (pharma, biotech, devices)
- Study start
- 12 Jun 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Oct 2024 (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, multi-center, single-dose Phase 1 clinical trial in subjects with transfusion dependent β-thalassaemia. The study aims to evaluate the safety and efficacy of autologous lentiviral-transduced CD34+ human hematopoietic stem cells (hHSCs) using the gene therapy product HGI-001.
Detailed description
The investigators will recruit transfusion-dependent β-thalassaemia patients and collect their autologous hematopoietic stem cells, which will be modified with the LentiHBBT87Q system to restore β-globin expression. After conditioning, the autologous hematopoietic stem cells with restored β-globin will be reinfused to the patients and followed up for two years to collect data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This phase 1 study employs a single-group, open-label design to evaluate the safety and preliminary efficacy of a gene therapy product. It is anticipated that 8 participants will be enrolled to receive a single administration of the investigational gene therapy. The primary focus will be on monitoring participants for adverse events and assessing the product's safety profile and potential therapeutic benefits.
| Arm | Type | Receives |
|---|---|---|
| β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q | Experimental | Other: β-globin restored autologous hematopoietic stem cellsThis arm involves the transduction of autologous hematopoietic stem cells with a lentiviral vector carrying the β-globin gene modified with LentiHBBT87Q. Subjects aged 6-35 years with transfusion-dependent β-thalassaemia will receive a infusion of these modified stem cells. |
Who may qualify
- Ages
- 6 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Aged 6-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
- Definitively diagnosed with severe TDT without genotype restriction (excluding patients with coexisting α-thalassemia), and a valid test report can be provided;
- Average transfusion volume > 100 mL/kg/year or transfusion frequency > 8 times/year within 2 years prior to enrollment；
- At least 3 months of full volume transfusion (verification of blood transfusion records can be provided) prior to screening, and Hb is maintained at ≥ 9.0 g/dL;
- Serum ferritin level less than 5000μg/L, with moderate or lower iron overload in the heart and liver as indicated by magnetic resonance imaging (MRI T2*), specifically liver MRI T2* greater than 1.4ms and cardiac MRI T2* greater than 10ms;
Key exclusion criteria (17 listed)
- Patients with fully HLA-matched donors;
- Having previously received gene therapy, gene editing therapy, or allogeneic hematopoietic stem cell transplantation;
- Uncorrected bleeding disorder;
- Uncontrolled epilepsy and mental illness;
- Within the past 3 months prior to enrollment, the use of Luspatercept, Hydroxyurea, Ruxolitinib, Thalidomide, Decitabine, or Ara-c has been administered；
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 |
|---|---|---|
| β-globin restored autologous hematopoietic stem cellsEight transfusion-dependent β-thalassaemia subjects aged 6-35 years will be reinfused with β-globin restored autologous hematopoietic stem cells modified with LentiHBBT87Q | Other | β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q |
Primary outcome
Transfusion Independence (TI) Rate
Time frame: 0-24 Months
Percent of subjects who achieve transfusion independence, defined as not requiring transfusion for at least 12 consecutive months post-HGI-001 injection, with a weighted average Hb of ≥ 9.0 g/dL. Calculated from the point hemoglobin reaches ≥9 g/dL and no transfusions have occurred in the last 60 days.
Incidence and Severity of Adverse Events (AEs) Related to Transplantation
Time frame: 0-24 Months
Number and percentage of adverse events related to transplantation, summarized according to NCI CTCAE 5.0.
Incidence of Serious Adverse Events (SAEs) Related to Transplantation
Time frame: 0-24 Months
Number of serious adverse events related to transplantation, summarized according to NCI CTCAE 5.0.
Overall Survival Rate During the Clinical Trial
Time frame: 0-24 Months
Number of patients alive throughout the entire trial period.
Percentage of Negative Replicating Lentivirus Test Post-HGI-001 Injection
Time frame: 0-24 Months
The percentage of participants with negative results for replicating lentivirus in the 24 months following HGI-001 injection.
Number of Participants with Normal Clonal Variations Post-Transplant
Time frame: 0-24 Months
Evaluation of the percentage of participants who do not exhibit abnormal clonal proliferation and maintain polyclonal engraftment following transplantation.
Number of Participants Experiencing Transplantation-related Fatal and Disabling Events Within 100 Days Post-transplantation
Time frame: 0-100Days
The number of participants who experience transplantation-related fatal and disabling events within 100 days after transplantation will be recorded and summarized.
Number of Patients with Abnormal Hematology and Bone Marrow Cytology Post-Reinfusion
Time frame: 0-24 Months
Number of patients exhibiting abnormal hematology and bone marrow cytology findings within 24 months after reinfusion, and the percentage of patients with abnormal RBC proliferation.
9 secondary outcomes
Percentage of Subjects Achieving Transfusion Cessation for Over 6 Months Post-HGI-001 Injection
Time frame: 0-24 Months
Percentage of Subjects with Successful HSC Engraftment
Time frame: 1 month
Percentage Change in Annual Transfusion Volume or Frequency
Time frame: 0-24 Months
Transfusion Improvement Rate
Time frame: 0-24 Months
Change in Vector Copy Number (VCN) Post-Transplantation
Time frame: 0-24 Months
Change in Exogenous Adult Hemoglobin HbAT87Q Expression Levels Post-Transplantation
Time frame: 0-24 Months
Changes in Cardiac and Liver Iron Load Post-HGI-001 Infusion
Time frame: 0-24 Months
Time to and Duration of Transfusion Independence in Subjects Post-HGI-001 Infusion
Time frame: 0-24 Months
Change in Serum Ferritin Levels Post-HGI-001 Infusion
Time frame: 0-24 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 23 Oct 2024.
- 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.
Chao Liu, PHD principal investigator
Shenzhen Hemogen
Sixi Liu, Professor principal investigator
Shenzhen Children's Hospital
Yongrong Lai, Professor principal investigator
First Affiliated Hospital of Guangxi Medical University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing β-globin restored autologous hematopoietic stem cells in people with Β-thalassemia, run by Shenzhen Hemogen at 3 sites 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 7 inclusion and 17 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 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Haigang Sun (13823168465, sunhaigang@genomics.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transfusion Independence (TI) Rate (time frame: 0-24 Months). The study lists 8 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 23 Oct 2024; AzTrials last refreshed its copy on 26 Oct 2026.