NCT07190001尚未招募1 期
An Exploratory Clinical Study to Evaluate the Safety and Efficacy of YOLT-204 in Patients With Hemoglobinopathies (β-thalassemia and Sickle-cell Disease)
Guangzhou Women and Children's Medical Center1 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2025年9月30日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Adverse event rate
研究概览
简要总结
This is a single-arm, open-label, single-dose, dose-escalation trial that plans to enrol 3-18 patients with transfusion-dependent β-thalassaemia (TDT) or sickle-cell disease (SCD). Its primary aims are to evaluate the safety and tolerability of a single administration of YOLT-204 and to obtain preliminary data on its effect on plasma fetal-haemoglobin levels. The main-study screening period may last up to 60 days; the treatment day is Day 0 (D0). Safety follow-up continues through Week 52 post-dose. After completion of the main study, participants will enter long-term follow-up extending to 15 years post-dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 3-17 years (inclusive); any sex.
- •The subject and/or his/her legally authorized guardian/representative must fully understand the study and voluntarily sign a written informed-consent form.
- •Karnofsky Performance Status (KPS) ≥ 70 (if ≥ 16 years old) or Lansky Performance Scale (LPS) ≥ 70 (if < 16 years old).
- •Detailed medical records of red-cell transfusions during the 2 years before informed-consent signature must be available, including volume or units transfused and pre-/post-transfusion red-cell and hemoglobin levels.
- •No severe hematopoietic dysfunction; cardiac, pulmonary, hepatic, and renal function essentially normal.
- •Coagulation: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN).
- •Renal function: serum creatinine ≤ 1.5 × ULN; if creatinine > 1.5 × ULN, calculated creatinine clearance > 50 mL/min by the Schwartz formula.
- •Hepatic function: alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN.
- •Cardiac function: left-ventricular ejection fraction (LVEF) ≥ 50 %.
- •Good compliance; willing to adhere to visit schedules, study procedures, laboratory tests, and other protocol requirements.
- •Agrees to use at least one highly effective contraceptive method from informed-consent signature through the end of the main study (Week 52 visit).
- •Willing to participate in long-term follow-up.
- •Screening genotype shows HbSS or HbSβ0; prior reports acceptable if assessed as adequate by the investigator.
- •If on L-glutamine, regimen must have been stable for ≥ 3 months before study-drug administration; if on hydroxyurea, must have discontinued ≥ 8 weeks before study-drug administration.
- •Meets severe SCD criteria: despite optimal supportive therapy (including, but not limited to, analgesics and hydroxyurea), at least two of the following events occurred in the 12 months before screening:
- •Severe intermittent acute pain requiring healthcare-provider management;
- •Acute chest syndrome with new pulmonary infiltrate on chest imaging plus pneumonia-like symptoms, pain, or fever;
- •Splenic sequestration crisis manifested by enlarged spleen, left upper-quadrant pain, and acute Hb drop > 20 g/L.
排除标准
- •1.History of multiple drug allergies or hypersensitivity to oligonucleotides or lipid nanoparticles (LNP).
- •2.Clinically significant active bacterial, viral, fungal, or parasitic infection at screening, as judged by the investigator.
- •3.White blood cell (WBC) count < 3 × 10⁹/L and/or platelet count < 100 × 10⁹/L at screening.
- •4.Uncorrected bleeding diathesis. 5.Massive splenomegaly at screening (spleen edge below the umbilicus or > 4 cm below the costal margin) deemed by the investigator to preclude enrollment.
- •6.Serum ferritin ≥ 5 000 ng/mL, or MRI T2* evidence of severe cardiac or hepatic iron overload.
- •7.Positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody, anti-HIV antibody, or specific anti-Treponema pallidum antibody.
- •8.Prior hematopoietic stem-cell transplantation, gene therapy, or gene-editing therapy.
- •9.Participation in another clinical trial and receipt of investigational product within 3 months before first dose of study drug.
- •10.Current or prior malignancy, myeloproliferative disorder, or immunodeficiency disease.
- •11.Severe psychiatric illness precluding cooperation; clinically significant pulmonary hypertension requiring medical intervention; recent malaria; first-degree relative with hematologic malignancy.
- •12.Positive pregnancy test, pregnancy, or lactation in female subjects at screening.
- •13.Any condition (past or present) that, in the investigator's opinion, could confound results, compromise participation, or render the patient unsuitable for the study.
- •14.Use within 3 months before study drug: erythropoietin (EPO), thalidomide, hydroxyurea, luspatercept, or similar agents.
- •15.In subjects ≥ 12 years, abnormal transcranial Doppler (TCD) with middle cerebral or internal carotid artery velocity ≥ 200 cm/s.
- •16.History of moyamoya disease or imaging findings consistent with moyamoya at screening, assessed by the investigator as conferring bleeding risk.
研究组 & 干预措施
Arms
Experimental
The intervention group will receive YOLT-204 on day0
干预措施: YOLT-204 (Drug)
结局指标
主要结局
Adverse event rate
时间窗: From baseline to 52 weeks after dose
Calculate the rate of various adverse events
3 months of sustained HbF level ≥20%
时间窗: From baseline to 52 weeks after dose
Proportion of patients who, starting one month after YOLT-204 treatment and without concomitant hydroxyurea, maintain HbF ≥ 20 % for at least three consecutive months.
3 months of sustained transfusion reduction
时间窗: From baseline to 52 weeks 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.
次要结局
- Concentration of Hemoglobin(From baseline to 52 weeks after dose)
- The proportion of alleles with intended modifications(From baseline to 52 weeks after dose)
- 6 months of sustained transfusion reduction(From baseline to 52 weeks after dose)
- Concentration of Fetal hemoglobin(From baseline to 52 weeks after dose)
- Concentration of proportion of F cell(From baseline to 52 weeks after dose)
- 3 months of transfusion independence(From baseline to 52 weeks after dose)
- 6 months of transfusion independence(From baseline to 52 weeks after dose)
- Free of hospitalization due to vaso-occlusive crisis(From baseline to 52 weeks after dose)
- Free of any vaso-occlusive crisis(From baseline to 52 weeks after dose)
- Change of red-blood-cell transfusions given(From baseline to 52 weeks after dose)
- The number of vaso-occlusive crises(From baseline to 52 weeks after dose)
研究者
研究点 (1)
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