Clinical Study on the Safety and Efficacy of an Intravenous Infusion of NGGT003 in the Treatment of Hemophilia A
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This is an early phase 1, open-label, single-center, dose-escalation pilot trial to evaluate the safety and efficacy of an intravenous infusion of NGGT003 in hemophilia A patients. NGGT003 uses adeno-associated virus (AAV) as a vector, carrying a liver specific promoter and codon optimized human FVIII gene B domain deletion mutant (hFVIII BDD), and expresses human FVIII protein in the liver through intravenous injection.
详细描述
Hemophilia A (HA) is an X-linked recessive genetic disease caused by mutations in the FVIII gene on the X chromosome, leading to abnormal coagulation function. In the male population, the incidence rate of hemophilia A was about 1/5000, and female patients with hemophilia A were extremely rare. Type A hemophilia patients mainly exhibit a tendency for bleeding, with a wide range of bleeding sites and frequent recurrence, which can form hematoma and joint deformation. This is an early phase 1, open-label, single-center, dose-escalation pilot trial to evaluate the safety and efficacy of a single intravenous infusion of NGGT003 in hemophilia A patients. 4-6 subjects will be enrolled and divided into 3 groups according to the principle of dose escalation, respectively administered intravenous infusion of NGGT003 at low dose (4e11vg/kg), medium dose (1e12vg/kg) and high dose (2.5e12vg/kg). All subjects will undergo 52 weeks of treatment observation and further 260 weeks of long-term follow-up.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form;
- •Male, age ≥18 years old;
- •Diagnosed with hemophilia A according to the "Guidelines for Diagnosis and Treatment of Hemophilia A (2022 Edition)", and the endogenous FVIII activity level was <1 IU/dL (<1%);
- •The exposure days (EDs) of treatment with any recombinant or plasma-derived FVIII product were ≥150 days;
- •Anti-AAV neutralizing antibody titer ≤1:5, binding antibody titer ≤1:100;
- •Bleeding events and/or FVIII product injections have occurred within 12 weeks before screening;
- •No history of allergy to FVIII products;
- •FVIII inhibitor titer﹤0.6BU/mL;
- •Commitment to use other drugs during the study requires the consent of the investigator;
- •Willing and able to comply with study procedures and requirements;
- •Willing to use effective contraceptive methods within 52 weeks after administration.
排除标准
- •Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV)，syphilis test;
- •Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) >1.5× ULN;TBil）>1.5×ULN；Serum creatinine (Scr) >1.5×ULN; hemoglobin <110g/L, platelets <10e9/L;
- •History of being positive for FVIII inhibitors;
- •Have other bleeding factors except hemophilia;
- •Plan major surgery within 52 weeks;
- •Have contraindications to glucocorticoid, including but not limited to allergy to glucocorticoids, epilepsy, new unhealed fractures, in trauma repair period, uncontrolled infection, severe osteoporosis, etc, which assessed and determined by the investigators;
- •History of allergy to human albumin;
- •Have serious diseases or active infections in cardiovascular, respiratory, digestive tract, endocrine, renal, blood, nervous, mental and other systems before screening;
- •With hepatitis, cirrhosis, liver cancer or other major liver diseases;
- •History of malignant tumors;
- •Abnormal and clinical significant vital signs, physical examination, laboratory examination or other related examination results during the screen, which are not suitable for trial according to the investigator;
- •Previous gene therapy treatment;
- •Participation in any other clinical trial before the screening and have taken medication within four weeks or five half-lives of the study drug;
- •Any other condition that may not be appropriate for the study in the opinion of the investigator.
研究组 & 干预措施
Experimental
3 doses of NGGT003 will be administered according to the principle of dose escalation
干预措施: NGGT003 (Drug)
结局指标
主要结局
Adverse events (AEs) and serious adverse events (SAEs)
时间窗: 52 weeks
Incidence of AE and SAE, as assessed by physical examinations, clinical laboratory parameters and adverse event reporting
Changes in annualized bleeding rate (ABR)
时间窗: 52 weeks
Changes in annualized bleeding rate (ABR) from baseline to 52 weeks.
次要结局
- FVIII activity levels(52 weeks)
- HA-QOL scores(52 weeks)
- FVIII protein product infusions(52 weeks)
- Target joints(52 weeks)