RecruitingNot ApplicableNCT06041620

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

A Study to Evaluate the Efficacy and Safety of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells in Transfusion-dependent β Thalassemia Patients


Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Enrollment

2 participants

Start Date

Aug 31, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 3 YearsMax Age: 35 Years

Inclusion Criteria8

  • 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.

Exclusion Criteria15

  • 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.

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Interventions

BIOLOGICALVGB-Ex01

CRISPR-Cas12b editing hematopoietic stem cells


Locations(1)

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

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NCT06041620


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