Evaluating a new gene therapy for transfusion-dependent beta-thalassemia

An Open Label Study Evaluating the Safety and Efficacy of Gene Therapy for Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a LentiRed Lentiviral Vector (GMCN-508B Drug Product, Also Called LentiRed)

This study is testing a new gene therapy to see if it can help people with transfusion-dependent beta-thalassemia reduce or stop their need for regular blood transfusions.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 5 Years to 35 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Guangxi Medical University (other)
• Locations: 1 site (Nanning, Guangxi)
• Trial ID: NCT05762510 on ClinicalTrials.gov

What this trial studies

This study is a single-arm, open-label, early-phase trial assessing the safety and efficacy of a gene therapy product called LentiRed in patients with transfusion-dependent beta-thalassemia. Participants will receive a single dose of autologous CD34+ human hematopoietic stem cells that have been modified with the LentiRed lentiviral vector. The study will monitor participants over a period of five years to evaluate treatment outcomes and safety. The goal is to determine if this innovative approach can reduce or eliminate the need for regular blood transfusions in affected individuals.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 5 to 35 with a clinical diagnosis of transfusion-dependent beta-thalassemia and a Karnofsky or Lansky performance score of 70 or higher.

Not a fit: Patients with active hepatitis B virus infection or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with transfusion-dependent beta-thalassemia by reducing or eliminating their dependence on blood transfusions.

How similar studies have performed: Other studies utilizing gene therapy approaches for beta-thalassemia have shown promising results, indicating potential success for this novel treatment.

Eligibility criteria

Inclusion Criteria:

1. The subject himself/herself or one legal guardian/agent of the subject is required to fully understand the study and voluntarily sign a written informed consent.
2. Ages 5 to 35, no gender limitation.
3. The clinical diagnosis of TDT includes β0/β0, β+/β0, βE/β0 and β+/β+ genotypes. TDT was defined as severe anemia in patients with thalassemia (Hb persistent \<70 g/L), regular RBC transfusion and standard iron removal therapy to survive for life.
4. Karnofsky Level of Performance (KPS) score ≥70 in adult subjects and Lansky Level of Performance (LPS) score ≥70 in children subjects.
5. Subjects were determined to undergo autologous hematopoietic stem cell transplantation by the principle investigator.
6. Subjects must have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion Criteria:

1. Hepatitis B virus (HBV) : HbsAg or HbcAb positive, nucleic acid test positive; Hepatitis C virus (HCV) : HCAb positive, nucleic acid test positive; Positive for Human immunodeficiency virus (HIV) antibody or Treponema pallidum (TP) specific antibody; Tuberculosis: positive interferon gamma release test.
2. A white blood cell (WBC) count \<3×10\^9/L and/or platelet count \<100×10\^9/L, splenectomy was performed before.
3. Uncured bleeding abnormalities.
4. Any previous or current malignancy, myeloproliferative disease, or immune deficiency disease.
5. Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndromes, hereditary non-polyposis colorectal cancer syndromes and familial adenomatous polyposis).
6. Previous hematopoietic stem cell transplantation (HSCT).
7. Advanced liver disease, defined as: 1) Baseline alanine aminotransferase (ALT) or direct bilirubin ≥3 normal upper limit (ULN), or 2) Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or acute hepatitis.
8. Baseline estimated glomerular filtration rate (eGFR) \< 70 mL/min /1.73 m2, as determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation for ≥18 years of age, and Besides Schwartz Equation calculator \< 18 years of age.
9. Uncontrolled seizure disorder.
10. Diffusion capacity of Carbon monoxide dispersion (DLco) \<50% of predicted (corrected for hemoglobin and or alveolar ventilation, as clinically indicated ).
11. A cardiac T2\* \<20 ms by magnetic resonance imaging (MRI).
12. Severe iron overload, which in the opinion of the physician is grounds for exclusion.
13. Clinically significant pulmonary hypertension.
14. Participation in another clinical study with an investigational drug within 30 days of screening.
15. Failure to obtain appropriate informed consent.
16. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or investigator.
17. Contraindications to the conditioning regimen.
18. Prior receipt of genetic stem cell therapy.
19. Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
20. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. Females of child-bearing potential are required to use effective contraception from the screening period until at least 6 months after drug product infusion. Male subjects are also required to use effective contraception (including condoms) from the screening period until at least 6 months after drug product infusion.
21. Live vaccines were administered within 6 weeks prior to screening.
22. Known history of hypersensitivity to the ingredients used in the trial.
23. An assessment by the investigator that the subject would not comply with the study procedures outlined in the protocol.

Where this trial is running

Nanning, Guangxi

• The affiliated hospital of guangxi medical university — Nanning, Guangxi, China (RECRUITING)

Study contacts

• Study coordinator: Yongrong Lai, PhD

Conditions: Transfusion Dependent Beta-Thalassemia, LentiRed, Beta-Thalassemia, Human Hematopoietic Stem Cell, gene therapy, CD34+