the Safety and Efficacy Evaluation of HGI-001 Injection in Patients With Transfusion-Dependent β-Thalassemia

NCT05864170 | Recruiting Early Phase 1

• 1 other identifier: HGI-001-CTP
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label study to evaluate the safety and efficacy of β-globin Restored Autologous Hematopoietic Stem Cells in ß-Thalassemia Major Patients

Conditions

β-thalassemia

Outcome Measures

Primary Outcomes (8)

• Overall response rate

  Percent of patients with average VCN \> 0.1 in peripheral blood mononuclear cells (PBMCs) and average expression of exogenous adult hemoglobin HbAT87Q \> 2.0 g/dL

  24 months

• Incidence and severity of AEs

  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

  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 day 100 after transplantation

  Transplantation-related fatal and disabling events

  Day 100

• Overall survival rate during the clinical trial

  Number of patients alive through the whole trial will be record

  0-24 months

• HGI-001 injection-related replicating lentivirus test

  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

  Evaluation of the percentage of participants without abnormal clonal proliferation and polyclonal engraftment at 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 and bone marrow cytology within 24 months after reinfusion, and percent of patients with abnormal RBC proliferation

  Number of patients with abnormal hematology and bone marrow cytology

  0-24 months

Secondary Outcomes (11)

• Treatment response rate

  12 Months

• Percent of subjects with successful HSC engraftment

  1 month

• Change in transfusion volume or frequency

  0-24 Months

• Transfusion improvement rate

  0-24 Months

• Transfusion independence (TI) rate

  0-24 Months

Study Arms (1)

Experimental

EXPERIMENTAL

Three transfusion-dependent β-thalassaemia subjects aged 18-35 years will be reinfused with β-globin restored autologous hematopoietic stem cells modified with LentiHBBT87Q

Biological: β-globin restored autologous hematopoietic stem cells

Interventions

β-globin restored autologous hematopoietic stem cells BIOLOGICAL

β-globin-restored autologous hematopoietic stem cells modified with LentiHBBT87Q

Experimental

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
• Definitively 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-001 injection.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shenzhen Hemogen: lead

Study Sites (1)

Shenzhen University General Hospital

Shenzhen, Guangdong, China

RECRUITING

Study Officials

• Chao Liu, PHD

  Shenzhen Hemogen

  PRINCIPAL INVESTIGATOR

• Li Yu

  Shenzhen University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haigang Sun

CONTACT

13823168465; sunhaigang@genomics.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: May 18, 2023
• Study Start: May 27, 2022
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: November 29, 2024

Record last verified: 2024-11

Locations

CN (1)