Evaluating Safety and Efficacy of Lentiviral-transduced CD34+ HSCs in Β-thalassaemia Patients.

NCT06655662 | Recruiting Phase 1 DMC

• 1 other identifier: HGI-001C04
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

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.

Conditions

Β-thalassemia

Keywords

β-thalassemia; Thalassemia; Genetic Diseases, Inborn; Hemoglobinopathies; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Congenital

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  0-24 Months

• Overall Survival Rate During the Clinical Trial

  Number of patients alive throughout the entire trial period.

  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.

  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.

  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.

  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.

  0-24 Months

Secondary Outcomes (9)

• 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

Study Arms (1)

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.

Other: β-globin restored autologous hematopoietic stem cells

Interventions

β-globin restored autologous hematopoietic stem cells OTHER

Eight transfusion-dependent β-thalassaemia subjects aged 6-35 years will be reinfused with β-globin restored autologous hematopoietic stem cells modified with LentiHBBT87Q

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

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Shenzhen Hemogen: lead

Study Sites (3)

Guangxi Medical University First Affiliated Hospital

Guangxi, China

RECRUITING

Shenzhen Children's Hospital

Shenzhen, China

RECRUITING

Shenzhen University General Hospital

Shenzhen, China

RECRUITING

MeSH Terms

Conditions

Thalassemia; Genetic Diseases, Inborn; Hemoglobinopathies; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Congenital

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Chao Liu, PHD

  Shenzhen Hemogen

  PRINCIPAL INVESTIGATOR

• Sixi Liu, Professor

  Shenzhen Children's Hospital

  PRINCIPAL INVESTIGATOR

• Yongrong Lai, Professor

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haigang Sun

CONTACT

13823168465; sunhaigang@genomics.cn

Linxia Qian

CONTACT

18851685852; qianlinxia@genomics.cn

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 23, 2024
• Study Start: June 12, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)