Clinical trial NCT06655662: Evaluating Safety and Efficacy of Lentiviral-transduced CD34+ HSCs in Β-thalassaemia Patients.
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Β-thalassemia
Keywords: β-thalassemia
Thalassemia
Genetic Diseases, Inborn
Hemoglobinopathies
Hematologic Diseases
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Lead sponsor: Shenzhen Hemogen
Sponsor class: INDUSTRY
First posted: 2024-10-23
Enrollment: 8
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Aged 6-35 years (inclusive), ICF can be provided by the patient and/or legal guardian;
2. Definitively diagnosed with severe TDT without genotype restriction (excluding patients with coexisting α-thalassemia), and a valid test report can be provided;
3. Average transfusion volume \> 100 mL/kg/year or transfusion frequency \> 8 times/year within 2 years prior to enrollment；
4. 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;
5. 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;
6. 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;
7. 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:

1. Patients with fully HLA-matched donors;
2. Having previously received gene therapy, gene editing therapy, or allogeneic hematopoietic stem cell transplantation;
3. Uncorrected bleeding disorder;
4. Uncontrolled epilepsy and mental illness;
5. Within the past 3 months prior to enrollment, the use of Luspatercept, Hydroxyurea, Ruxolitinib, Thalidomide, Decitabine, or Ara-c has been administered；
6. Psychoactive substance abuse, drug or alcohol abuse within 6 months prior to enrollment;
7. Patients with pulmonary hypertension who have not been given effective intervention;
8. Positive for anti-RBC antibodies in antibody screening;
9. 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；
10. Have or have had malignant tumors or myeloproliferative diseases or immunodeficiency disorders or autoimmune diseases;
11. 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);
12. Severe bacterial, viral, fungal or parasitic infection;
13. 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);
14. WBC \< 3 × 10\^9/L and/or PLT \< 100 × 10\^9/L;
15. Has diabetes, abnormal thyroid functions or other endocrine disorder;
16. Participated in other interventional clinical studies within 4 weeks before the trial;
17. Poor adherence or other conditions that renders the subject unsuitable for participation as judged by the investigator.

Primary outcomes:
measure: Transfusion Independence (TI) Rate
timeFrame: 0-24 Months
measure: Incidence and Severity of Adverse Events (AEs) Related to Transplantation
timeFrame: 0-24 Months
measure: Incidence of Serious Adverse Events (SAEs) Related to Transplantation
timeFrame: 0-24 Months
measure: Overall Survival Rate During the Clinical Trial
timeFrame: 0-24 Months
measure: Percentage of Negative Replicating Lentivirus Test Post-HGI-001 Injection
timeFrame: 0-24 Months
measure: Number of Participants with Normal Clonal Variations Post-Transplant
timeFrame: 0-24 Months
measure: Number of Participants Experiencing Transplantation-related Fatal and Disabling Events Within 100 Days Post-transplantation
timeFrame: 0-100Days
measure: Number of Patients with Abnormal Hematology and Bone Marrow Cytology Post-Reinfusion
timeFrame: 0-24 Months
Secondary outcomes:
measure: Percentage of Subjects Achieving Transfusion Cessation for Over 6 Months Post-HGI-001 Injection
timeFrame: 0-24 Months
measure: Percentage of Subjects with Successful HSC Engraftment
timeFrame: 1 month
measure: Percentage Change in Annual Transfusion Volume or Frequency
timeFrame: 0-24 Months
measure: Transfusion Improvement Rate
timeFrame: 0-24 Months
measure: Change in Vector Copy Number (VCN) Post-Transplantation
timeFrame: 0-24 Months
measure: Change in Exogenous Adult Hemoglobin HbAT87Q Expression Levels Post-Transplantation
timeFrame: 0-24 Months
measure: Changes in Cardiac and Liver Iron Load Post-HGI-001 Infusion
timeFrame: 0-24 Months
measure: Time to and Duration of Transfusion Independence in Subjects Post-HGI-001 Infusion
timeFrame: 0-24 Months
measure: Change in Serum Ferritin Levels Post-HGI-001 Infusion
timeFrame: 0-24 Months
Other outcomes:
Locations:
city: Guangxi
country: China
facility: Guangxi Medical University First Affiliated Hospital
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
city: Shenzhen
country: China
facility: Shenzhen University General Hospital
Study officials:
affiliation: Shenzhen Hemogen
name: Chao Liu, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen Children's Hospital
name: Sixi Liu, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Guangxi Medical University
name: Yongrong Lai, Professor
role: PRINCIPAL_INVESTIGATOR
References: