A Pilot Study on the Safety and Efficacy of YOLT-204 for Transfusion-Dependent Beta-Thalassemia

Launched by FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIVERSITY · Nov 5, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called YOLT-204 for people with transfusion-dependent beta-thalassemia, a condition where patients need regular blood transfusions because their bodies cannot produce enough healthy red blood cells. The trial aims to find out if a single dose of YOLT-204 is safe and how it might affect the levels of a type of hemoglobin (the protein in red blood cells that carries oxygen) in the blood. The study will enroll between 3 to 9 adult participants aged 18 to 35 who meet specific health criteria, including having a good level of overall health and no severe heart, liver, or kidney issues.

Participants can expect to receive YOLT-204 and will be monitored closely for any side effects. They will also need to provide detailed medical records about their previous blood transfusions. Importantly, this trial is not yet recruiting participants, but if you're interested, it will be essential to understand that certain medical conditions or past treatments might make someone ineligible to participate. This study represents an early step in exploring new options for managing beta-thalassemia, which could lead to better treatments in the future.

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Eligibility criteria

• • 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.