An Open, Multi-center, Phase I Clinical Study on the Safety and Efficacy of HGI-001 Injection in Patients with Transfusion-Dependent Β-Thalassemia.
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Β-thalassemia
- Sponsor
- Shenzhen Hemogen
- Enrollment
- 8
- Locations
- 3
- Primary Endpoint
- Transfusion Independence (TI) Rate
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
- •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;
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Change in Serum Ferritin Levels Post-HGI-001 Infusion(0-24 Months)
- Percentage of Subjects Achieving Transfusion Cessation for Over 6 Months Post-HGI-001 Injection(0-24 Months)
- Percentage of Subjects with Successful HSC Engraftment(1 month)
- Percentage Change in Annual Transfusion Volume or Frequency(0-24 Months)
- Transfusion Improvement Rate(0-24 Months)
- Change in Vector Copy Number (VCN) Post-Transplantation(0-24 Months)
- Change in Exogenous Adult Hemoglobin HbAT87Q Expression Levels Post-Transplantation(0-24 Months)
- Changes in Cardiac and Liver Iron Load Post-HGI-001 Infusion(0-24 Months)
- Time to and Duration of Transfusion Independence in Subjects Post-HGI-001 Infusion(0-24 Months)