- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05851105
the Safety and Efficacy Evaluation of HGI-002 Injection in Patients With Transfusion-Dependent α-Thalassemia
May 6, 2023 updated by: Shenzhen Hemogen
This is an open label study to evaluate the safety and efficacy of α-globin Restored Autologous Hematopoietic Stem Cells in α-Thalassemia Major Patients
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
3
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Haigang Sun
- Phone Number: 13823168465
- Email: sunhaigang@genomics.cn
Study Locations
-
-
Guangxi
-
Nanning, Guangxi, China
- Recruiting
- PLA Joint Logistic Support Force No. 923 Hospital
-
Contact:
- Haigang Sun
- Phone Number: 13823168465
- Email: sunhaigang@genomics.cn
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Aged 12-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
- Definitively α- thalassemia diagnosed with severe TDT without genotype restriction, 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, or has been definitively diagnosed with TDT;
- 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;
- Ferritin load < 3000 μg/L, cardiac and liver iron indicates moderate or lesser iron overload; records of iron chelation treatments within 3 months before screening (including prescription or receipt) can be provided;
- 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-002 injection.
Exclusion Criteria:
- Patients with fully HLA-matched donors;
- Received allogeneic transplantation, which needs to be weighed and evaluated by an expert committee; received other gene therapies;
- Have previously undergone splenectomy;
- Uncorrected bleeding disorder;
- Uncontrolled epilepsy and mental illness;
- Received hydroxyurea, ruxolitinib, decitabine, or cytarabine within 3 months prior to enrollment;
- Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
- Patients with pulmonary hypertension who have not been given effective intervention;
- Persistent toxicity (≥ CTCAE grade 2) induced by previous treatment;
- Positive for anti-RBC antibodies in antibody screening;
- Positive for hepatitis B surface antigen (HBsAg) and HBV DNA copy number > upper limit of normal (ULN) (HBV DNA test not required for patients negative for HBsAg), positive for hepatitis C virus (HCV) antibody, positive human immunodeficiency virus (HIV), or positive for Treponema pallidum antibody (TP-Ab) (subjects who are positive for the antibody due to vaccination can be enrolled). In certain clinical environments/regions, subjects who are positive for other tests can also be excluded from the trial, such as, human lymphocytic virus-1 (HTLV-1) or -2 (HTLV-2), tuberculosis, and toxoplasmosis.
- Has or has had malignant tumors or myeloproliferative disease or immunodeficiency disease;
- Immediate family member with or suspected of having a familial cancer (including but not limited to hereditary breast and ovarian cancers, 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 < 30% of normal;
- WBC < 3 × 109/L and/or PLT < 100 × 109/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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental
Three transfusion-dependent α-thalassaemia subjects aged 12-35 years will be reinfused with α-globin restored autologous hematopoietic stem cells modified with LentiHBA T>C
|
α-globin restored autologous hematopoietic stem cells modified with LentiHBA T>C
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate
Time Frame: 0-24 months
|
Percent of patients with average VCN > 0.1 in peripheral blood mononuclear cells
|
0-24 months
|
Incidence and severity of AEs
Time Frame: 0-24 months
|
The number and the percentage of adverse events related to transplantation will be summarized according to NCI CTCAE 5.0
|
0-24 months
|
incidence of SAEs
Time Frame: 0-24 months
|
The number of SAE related to transplantation will be summarized according to NCI CTCAE 5.0
|
0-24 months
|
Transplantation-related fatal and disabling events within 100 d after transplantation
Time Frame: Day 100
|
Transplantation-related fatal and disabling events
|
Day 100
|
Overall survival rate during the clinical trial
Time Frame: 0-24 months
|
Number of patients alive through the whole trial will be record
|
0-24 months
|
HGI-002 injection-related replicating lentivirus test
Time Frame: 0-24 months
|
The percentage of RCL should be negative in the 24 months after transplant
|
0-24 months
|
Change from baseline in Clonal variations containing specific viral integration sites
Time Frame: 0-24 months
|
Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment at baseline, 6, 12, 18 and 24 months after transplant.
More than 1000 VIS retrieved from peripheral blood should be checked.
|
0-24 months
|
Number of patients with abnormal hematology cytology and bone marrow cytology within 24 months after reinfusion
Time Frame: 0-24 months
|
Number of patients with abnormal hematology cytology and bone marrow cytology
|
0-24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment response rate
Time Frame: 12 Months
|
Percent of patients with average VCN > 0.1 in PBMCs
|
12 Months
|
Percent of subjects with successful HSC engraftment
Time Frame: 1 month
|
Criteria for successful engraftment: Absolute neutrophil count > 0.5 × 10 9 /L for 3 consecutive days; platelet count is maintained at > 20 × 10 9 /L for 7 consecutive days without platelet transfusion
|
1 month
|
Change in transfusion volume or frequency
Time Frame: 0-24 Months
|
Change in average annual transfusion volume or frequency from baseline or change in percentage
|
0-24 Months
|
Transfusion improvement rate
Time Frame: 0-24 Months
|
Percent of subjects with ≥ 30% decrease in the average annual (0-12 months, 12-24 months) transfusion volume or frequency from baseline after reinfusion of HGI-002 injection
|
0-24 Months
|
Transfusion independence (TI) rate
Time Frame: 0-24 Months
|
Percent of subjects who do not require transfusion for at least 12 consecutive months after reinfusion of HGI-002 injection and have a weighted average Hb of ≥ 9.0 g/dL
|
0-24 Months
|
Transfusion-free survival
Time Frame: 0-24 Months
|
the time when a subject meets the TI criteria and maintains transfusion-free survival
|
0-24 Months
|
Changes in VCN
Time Frame: 0-24 Months
|
Vector copy number
|
0-24 Months
|
Changes in cardiac iron load after reinfusion of HGI-002 injection
Time Frame: 0-24 Months
|
T2 MRI
|
0-24 Months
|
Changes in liver iron load after reinfusion of HGI-002 injection
Time Frame: 0-24 Months
|
T2 MRI
|
0-24 Months
|
Changes in serum ferritin after reinfusion of HGI-002 injection
Time Frame: 0-24 Months
|
serum ferritin
|
0-24 Months
|
Changes use of iron chelation medications after reinfusion of HGI-002 injection
Time Frame: 0-24 Months
|
iron chelation medications
|
0-24 Months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Chao Liu, PHD, Shenzhen Hemogen
- Principal Investigator: Xinhua Zhang, PLA Joint Logistic Support Force No. 923 Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 8, 2022
Primary Completion (Anticipated)
March 1, 2025
Study Completion (Anticipated)
December 1, 2025
Study Registration Dates
First Submitted
February 28, 2023
First Submitted That Met QC Criteria
May 6, 2023
First Posted (Actual)
May 9, 2023
Study Record Updates
Last Update Posted (Actual)
May 9, 2023
Last Update Submitted That Met QC Criteria
May 6, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HGI-002-C01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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