Safety and Dose Finding Study of KL001 in Moderately Severe to Severe Hemophilia B Subjects
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 主要终点
- Incidence of treatment- related adverse events
研究概览
简要总结
This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL001 injection solution in hemophilia B subjects with ≤2 IU/dl residual FIX levels.
详细描述
This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL001 injection solution in hemophilia B subjects with ≤2 IU/dl residual FIX levels. Nine subjects will be enrolled and administered with three different doses of KL001. Subjects will provide informed consent and then undergo screening assessments up to 1 month prior administration of KL001. All subjects will undergo 52 weeks safety observation and will be encouraged to enroll in an extension study to evaluate long- term safety of KL001 for total 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male ≥12 years of age.
- •Moderate/severe or severe hemophilia B (baseline FIX activity ≤2% of normal or documented history of FIX activity ≤2%).
- •At least 3 bleeding episodes per year that require on-demand treatment with FIX or are treated with a prophylactic regimen of FIX.
- •At least 100 days exposure history to recombinant or plasma-derived FIX protein products.
- •No neutralizing antibodies to exogenous FIX protein products.
- •Willing and able to comply with study procedures and requirements.
排除标准
- •Suffering from chronic inflammatory muscle disease.
- •Positive in Hepatitis B or Hepatitis C.
- •Infection with HIV-1 or HIV-2 and CD4+T cell count ≤ 200/ μ L.
- •History of thrombosis or susceptibility to thrombosis.
- •Current or previous participation in another gene therapy study.
- •Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.
研究组 & 干预措施
KL001 injection solution
Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10^12 vg/kg to 1.0x10^13 vg/kg.
干预措施: Low dose KL001 (Drug)
KL001 injection solution
Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10^12 vg/kg to 1.0x10^13 vg/kg.
干预措施: Middle dose KL001 (Drug)
KL001 injection solution
Subjects will be dosed with three different dose of KL001 injection solution at 2.5x10^12 vg/kg to 1.0x10^13 vg/kg.
干预措施: High dose KL001 (Drug)
结局指标
主要结局
Incidence of treatment- related adverse events
时间窗: Infusion to the completion of study, about 52 weeks
Number and severity of adverse events and serious adverse events and relationship to KL001
Antibody against KL001 AAV vector capsid protein
时间窗: Infusion to the completion of study, about 52 weeks
Immune response against AAV capsid will be evaluated by measurement of the total antibody and neutralizing antibody against AAV capsid protein in plasma samples collected at multiple timepoints after dosing up to 52 weeks
Factor IX inhibitor
时间窗: Infusion to the completion of study, about 52 weeks
Development of inhibitor against vector-derived Factor IX protein will be measured using bethesda method.
次要结局
- vector-derived FIX: C activity levels(From dosing day to week 52)
- The annualized bleeding rate Before and After KL001 Infusion(From dosing day to week 52)
- The annualized use of FIX(From dosing day to week 52)
研究者
Liang Liang
associate chief physician
Affiliated Hospital of Guangdong Medical University