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

Обзор

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

Вмешательства

• Препарат YOLT-204
  The intervention group will receive YOLT-204 on day0

Первичные конечные точки

• Treatment-Emergent Adverse Events [Срок оценки: 52 weeks after dose]
• Laboratory Test Findings [Срок оценки: 52 weeks after dose]
• Safety Measurements [Срок оценки: 52 weeks after dose]
• 3 months of sustained transfusion reduction [Срок оценки: 4 months after dose]
• 3 months of transfusion independence [Срок оценки: 4 months after dose]

Вторичные конечные точки (5)

• 6 months of sustained transfusion reduction [Срок оценки: 7 months after dose]
• 6 months of transfusion independence [Срок оценки: 7 months after dose]
• The proportion of alleles with intended modifications [Срок оценки: 52 weeks after dose]
• Fetal hemoglobin concentration [Срок оценки: 52 weeks after dose]
• Total hemoglobin concentration [Срок оценки: 52 weeks after dose]

Критерии участия

Inclusion Criteria：

• Age between 18 to 35 years, gender not limited.
• The patient has fully understood this study and voluntarily signed an informed consent form.
• Clinically diagnosed as a patient with transfusion-dependent β-thalassemia, excluding the genotype: β0β0.
• Karnofsky Performance Status (KPS) score of at least 70.
• 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.
• No severe hematopoietic dysfunction, with heart, lung, liver, and kidney functions essentially normal.
• Coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) both ≤1.5×ULN (Upper Limit of Normal).
• 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).
• Liver function: Alanine Aminotransferase (ALT) ≤3×ULN and Aspartate Aminotransferase (AST) ≤3×ULN; Direct Bilirubin ≤2.5×ULN.
• Cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50%.
• Good compliance, willing to adhere to visit schedules, trial plans, laboratory tests, and other trial steps.
• Willing to participate in long-term follow-up studies.

Критерии исключения

• History of multiple drug allergies or a history of allergic reactions to oligonucleotides or lipid nanoparticles (LNPs).
• Diagnosed with compound alpha-thalassemia.
• Clinically significant active bacterial, viral, fungal, or parasitic infections at the time of screening, as judged by the investigator.
• 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.
• Uncorrected bleeding disorders.
• Received treatment with erythropoietin (EPO) within the three months prior to enrollment.
• Severe iron overload, with serum ferritin levels ≥5000 ng/ml.
• 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).
• History of hematopoietic stem cell transplantation, gene therapy, or gene editing therapy.
• Participation in another clinical study and use of investigational drugs within 3 months prior to starting the study drug.
• History or current presence of malignant tumors or myeloproliferative diseases or immunodeficiency diseases.
• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Guangxi Medical University — Nanning

Идентификаторы

NCT: NCT06678165 · YOLT-204-IIT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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