Evaluating the safety and effectiveness of edited stem cells for treating beta thalassemia

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

This study is testing if a new treatment using edited stem cells can help people with beta thalassemia produce healthier red blood cells and reduce their need for blood transfusions.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 2 (estimated)
• Ages: 3 Years to 35 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06041620 on ClinicalTrials.gov

What this trial studies

This exploratory clinical study aims to assess the safety and efficacy of autologous CRISPR-Cas12b edited hematopoietic stem cells in patients with transfusion-dependent beta thalassemia. The study involves a single injection of the edited stem cells, which are designed to reactivate gamma-globin and induce fetal hemoglobin expression, thereby improving red blood cell production and survival. Participants will be monitored continuously for safety and efficacy, with follow-up extending up to 24 months. After the trial, participants may join a long-term follow-up study lasting 15 years.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 3-35 years with a clinical diagnosis of transfusion-dependent beta thalassemia and a history of significant blood transfusions.

Not a fit: Patients who are not transfusion-dependent or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the need for blood transfusions in patients with beta thalassemia.

How similar studies have performed: While the use of CRISPR technology in hematopoietic stem cells is a novel approach, similar studies have shown promise in gene editing for blood disorders.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Tianjin, Tianjin Municipality

• Regenerative Medicine Center — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jun Shi, PhD — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Jun Shi, PhD

Conditions Thalassemia, Beta; Thalassemia Major