Safety and Efficacy Evaluation of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells

NCT06041620 | Recruiting

• 1 other identifier: VGB-Ex01-001
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open, single-injection exploratory clinical study with two transfusion-dependent β thalassemia (β-TDT) participants planned to enroll.

Conditions

Thalassemia, Beta; Thalassemia Major

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events and serious adverse events

  An adverse event is any untoward medical occurrence in a clinical investigation/participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.

  Baseline up to 24 months

• Number of subjects with neutrophil implantation ≤ 42 days

  Neutrophil implantation was defined as 3 consecutive days with 3 tests for ANC≥500/μL.

  Baseline up to 42 days

Secondary Outcomes (5)

• Number of subjects transfusion independence (TI) for at least 6 months after transfusion

  Baseline up to 6 months

• Number of subjects transfusion independence (TI) for at least 12 months after transfusion

  Baseline up to 12 months

• Fetal hemoglobin (HbF) concentration

  Baseline up to 24 months

• Total hemoglobin (Hb) concentration

  Baseline up to 24 months

• The proportion of circulating red blood cells

  Baseline up to 24 months

Study Arms (1)

VGB-Ex01

EXPERIMENTAL

Each subject will accept one dose of VGB-Ex01.

Biological: VGB-Ex01

Interventions

VGB-Ex01 BIOLOGICAL

CRISPR-Cas12b editing hematopoietic stem cells

VGB-Ex01

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 3-35 years old (inclusive), male or female;
• The subject and/or his/her legally recognized representative/parent/guardian fully understands the study and all information related to the study and has signed the informed consent form;
• Clinical diagnosis of transfusion-dependent β-thalassemia (TDT) with a blood transfusion record within 2 years (inclusive) prior to screening showing a history of ≥ 10 units (U)/kg/year (or ≥ 100 mL/kg/year) or ≥ 8 times/year of suspended RBC transfusions in at least 1 consecutive 12-month period;
• Karnofsky score (for subjects aged ≥ 16 years) or Lansky score (for subjects aged \< 16 years) of ≥ 80;
• Subjects in stable disease state who are eligible for hematopoietic stem cell transplantation as per investigator's judgment;
• Access to diagnosis and treatment records issued by medical professional institutions within 2 years prior to screening, including the records of blood transfusions, hematology, serum chemistry, and other examinations;
• Willing and able to comply with study procedures, with good compliance, and willing to receive and complete the follow-up study with a duration of at least 2 years;
• Subjects of childbearing potential (including female subjects of childbearing potential and male subjects whose partners are of childbearing potential) must use effective contraception within 12 months of treatment.

You may not qualify if:

• Diagnosis of associated α-thalassemia: \> 1 alpha chain deletion or alpha gene functional defect;
• Have available HLA-fully matched donors and acceptable for allogeneic hematopoietic stem cell transplantation;
• Irregular antibody or platelet antibody positive;
• Prior allogeneic bone marrow transplantation or gene therapy;
• Subjects with clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator at screening, including but not limited to those with positive etiology of human immunodeficiency virus (HIV-1/2), human cytomegalovirus (HCMV-DNA), Epstein-Barr virus (EBV-DNA), or Treponema pallidum antibody (TP-Ab), or with previous hepatitis B or C infection;
• Subjects with an injury of major organs
• Contraindications for hematopoietic stem cell collection and poor collection efficiency judged by the investigator;
• Contraindications to the clinical investigational product and its excipients, G-CSF (hematopoietic stem cell mobilization), plerixafor (hematopoietic stem cell mobilization), busulfan (myeloablation), and other drugs;
• Participation within 3 months prior to screening or current participation in another interventional clinical study;
• History or family history of malignancy or myeloproliferative disorder;
• History of uncontrollable epilepsy, mental disorder, or other psychiatric disorders;
• Abuse of psychoactive substance, drug, or alcohol within 6 months prior to enrollment;
• Pregnant or breastfeeding females;
• Other diseases or reasons that interfere with study procedures;
• Any other conditions that the investigator deems unsuitable for the subject's participation in the study.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Shanghai Vitalgen BioPharma Co., Ltd.: collaborator

Study Sites (1)

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jun Shi, PhD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Shi, PhD

CONTACT

13752253515; shijun@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Regenerative Medical Center

Study Record Dates

• First Submitted: September 11, 2023
• First Posted: September 18, 2023
• Study Start: August 31, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)