Transfusion Dependent Beta Thalassemia
Conditions
Brief summary
This study is a single-arm, open-label, dose-escalation trial, planning to enroll 3-9 patients with transfusion-dependent β-thalassemia, aimed at assessing the safety and tolerability of a single-dose of YOLT-204 in patients with transfusion-dependent β-thalassemia; to preliminarily evaluate the impact of a single -dose of YOLT-204 on the levels of fetal hemoglobin in the plasma
Interventions
DRUGYOLT-204
The intervention group will receive YOLT-204 on day0
Sponsors
First Affiliated Hospital of Guangxi Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
： 1. Age between 18 to 35 years, gender not limited. 2. The patient has fully understood this study and voluntarily signed an informed consent form. 3. Clinically diagnosed as a patient with transfusion-dependent β-thalassemia, excluding the genotype: β0β0. 4. Karnofsky Performance Status (KPS) score of at least 70. 5. Obtain detailed medical records of red blood cell transfusions within 2 years prior to the patient signing the informed consent form, including the volume or units of transfusion and the levels of red blood cells and hemoglobin before and after transfusion. 6. No severe hematopoietic dysfunction, with heart, lung, liver, and kidney functions essentially normal. 7. Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) both ≤1.5×ULN (Upper Limit of Normal). 8. Renal function: Creatinine ≤1.5×ULN, or when creatinine \>1.5×ULN, the creatinine clearance is \>50ml/min (calculated according to the Cockcroft-Gault formula). 9. Liver function: Alanine Aminotransferase (ALT) ≤3×ULN and Aspartate Aminotransferase (AST) ≤3×ULN; Direct Bilirubin ≤2.5×ULN. 10. Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50%. 11. Good compliance, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial steps. 12. Willing to participate in long-term follow-up studies.
Exclusion criteria
1. History of multiple drug allergies or a history of allergic reactions to oligonucleotides or lipid nanoparticles (LNPs). 2. Diagnosed with compound alpha-thalassemia. 3. Clinically significant active bacterial, viral, fungal, or parasitic infections at the time of screening, as judged by the investigator. 4. White blood cell count (WBC) \<3×10\^9/L and/or platelet count \<100×10\^9/L not due to hypersplenism, as judged by the investigator. 5. Uncorrected bleeding disorders. 6. Received treatment with erythropoietin (EPO) within the three months prior to enrollment. 7. Severe iron overload, with serum ferritin levels ≥5000 ng/ml. 8. Positive for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus, antibodies to human immunodeficiency virus (HIV), or specific antibodies to Treponema pallidum (syphilis). 9. History of hematopoietic stem cell transplantation, gene therapy, or gene editing therapy. 10. Participation in another clinical study and use of investigational drugs within 3 months prior to starting the study drug. 11. History or current presence of malignant tumors or myeloproliferative diseases or immunodeficiency diseases. 12. Presence of severe mental illness that prevents cooperation with treatment; significant pulmonary arterial hypertension requiring medical intervention; recent malaria; a history of hematological tumors in immediate family members. 13. Any past or current disease, treatment, or laboratory abnormality that may interfere with the study results, affect the patient's full participation in the study, or that the investigator deems unsuitable for participation in this clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3 months of transfusion independence | 4 months after dose | Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 3 months of transfusion independence (sustained TI3) is obtained. |
| Treatment-Emergent Adverse Events | 52 weeks after dose | Number of Participants with Treatment-Emergent Adverse Events |
| Laboratory Test Findings | 52 weeks after dose | Number of Participants with Clinically Significant Clinical Laboratory Test Findings |
| Safety Measurements | 52 weeks after dose | Number of Participants with Clinically Significant Safety Measurements |
| 3 months of sustained transfusion reduction | 4 months after dose | Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 3 months of sustained transfusion reduction (sustained TR3) is obtained. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 months of sustained transfusion reduction | 7 months after dose | Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 6 months of sustained transfusion reduction (sustained TR6) is obtained. |
| 6 months of transfusion independence | 7 months after dose | Analysis begins one month after treatment with YOLT-204, and the proportion of patients who achieve at least 6 months of transfusion independence (sustained TI6) is obtained. |
| The proportion of alleles with intended modifications | 52 weeks after dose | The proportion of alleles with intended modifications in peripheral blood leukocytes and bone marrow cells over time. |
| Fetal hemoglobin concentration | 52 weeks after dose | The change in fetal hemoglobin concentration over time after YOLT-204 infusion |
| Total hemoglobin concentration | 52 weeks after dose | The change in total hemoglobin concentration over time after YOLT-204 infusion. |
Countries
China
Contacts
Primary ContactRongrong Liu
Outcome results
None listed