A Single-arm, Open-label Study Evaluating the Safety and Efficacy of a Single Dose of GS1191-0445 Injection in Chinese Subjects With Severe Hemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- The Change of Laboratory Values: Change in serum chemistry values including liver function tests, hematology, and urinalysis;
研究概览
简要总结
This study is a single-arm, open-label study evaluating the safety and efficacy of GS1191-0445 injection as a single dose in Chinese subjects with severe hemophilia A.
GS1191-0445 is an adeno-associated virus 8 (AAV8)-delivered gene therapy designed to express B-domain deleted human factor VIII (FVIII) under the regulation of a human liver-specific promoter. Following a single intravenous administration, AAV8 gene expression cassette, which transfects hepatocytes and facilitates the specific expression and secretion of FVIII into the blood.
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 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Understand the purpose and risks of the study and provide informed consent in accordance with national and local privacy laws:
- •Subject must be male, aged ≥18 years old at the time of signing informed consent:
- •Participants with confirmed severe hemophilia A in their pre-admission history and based on clinical laboratory examination;
- •Subjects had used FVIII products for at least 150 exposure days (ED) before enrollment;
- •Subject has received continuous prophylactic treatment with exogenous FVIII for one year prior to enrollment or has been treated with exogenous FVIII on demand;
- •Subject has no history of hypersensitivity or allergic reactions related to the administration of FVIII agents;
- •Subject has no history of FVIII inhibitors.
- •Subjects agree to use a reliable barrier contraceptive method from the date of signing the informed consent
- •Subject is willing and able to follow planned visits, treatment plans, and other study procedures.
排除标准
- •The subject has any hemorrhagic disorder not related to hemophilia A,
- •Abnormal liver function test results of subjects during screening.
- •Abnormal laboratory examination of subjects during screening
- •The subject has acute or chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; Or are receiving antiviral treatment for hepatitis B and C;
- •Active systemic immune disease.
研究组 & 干预措施
3E12 vg/kg
干预措施: GS1191-0445 injection (Drug)
结局指标
主要结局
The Change of Laboratory Values: Change in serum chemistry values including liver function tests, hematology, and urinalysis;
时间窗: Five years after infusion
FVIII inhibitor: Factor VIII inhibitor will be measured to determine the immunogenicity of FVIII expression protein;
时间窗: Five years after infusion
Number of participants with Adverse Events (AE) as assessed by CTCAE v5.0, including Adverse Event of Special Interests (AESI) and Serious Adverse Events (SAE);
时间窗: Five years after infusion
Number of Participants with Thrombosis Risk: In subjects with >150% FVIII:C post-GS1191-0445 infusion, VTE risk will be assessed via Caprini model, coagulation function, D-dimer, FDP, and TAT;
时间窗: Five years after infusion
The shedding of GS1191-0445 viral vector: Viral vector titers in serum, saliva, urine, semen and fecal will be monitored;
时间窗: Five years after infusion
Total FVIII Antibody Levels: Total FVIII antibody levels will be measured to determine the immunogenicity of FVIII expression protein;
时间窗: Five years after infusion
The number of dose-limiting toxicity (DLT) events will be determined by the Safety Review Committee (SRC), at least 12 weeks after GS1191-0445 infusion.
时间窗: Five years after infusion
Changes for vital signs: Includes sitting blood pressure (mmHg), respiratory rate (breaths/min), body temperature (°C), and pulse rate (beats/min);
时间窗: Five years after infusion
Changes for physical examination: Includes skin, mucous membranes, lymph nodes, head and neck, chest (heart, lungs), abdomen, muscles, nervous system, spine/extremities;
时间窗: Five years after infusion
The immunogenicity of AAV capsid protein: Collection of Peripheral Blood Mononuclear Cell (PBMC) and serum samples for vector shedding detection;
时间窗: Five years after infusion
Total FⅧ Antibody Levels: Total FⅧ antibody levels will be measured to determine the immunogenicity of FⅧ expression protein;
时间窗: Five years after infusion
Number of Participants with Thrombosis Risk: In subjects with >150% FⅧ:C post-GS1191-0445 infusion, VTE risk will be assessed via Caprini model, coagulation function, D-dimer, FDP, and TAT;
时间窗: Five years after infusion
FVIII inhibitor: Factor Ⅷ inhibitor will be measured to determine the immunogenicity of FⅧ expression protein;
时间窗: Five years after infusion
次要结局
- Vector-derived FVIII Activity Level: Validated methods will be used to measure vector-derived FVIII activity, including peak and steady state following GS1191-0445 infusion；(Day 4 to Week 52 after infusion)
- Total Consumption of Exogenous FVIII Infusion;(Weeks 3 to 52 and five years after infusion)
- Annualized Consumption of FVIII Infusion；(Weeks 3 to 52 and five years after infusion)
- Number of bleeding events requiring exogenous FVIII infusion: To assess the number of bleeding events requiring exogenous FVIII infusion after administration;(Weeks 3 to 52 and five years after infusion)
- Number of bleeding events: To assess bleeding events, including spontaneous, traumatic and untreated bleeding events after administration(Weeks 3 to 52 and five years after infusion)
- Number of joint bleeding events: To assess joint bleeding events after administratio(Weeks 3 to 52 and five years after infusion)
- Vector-derived FⅧ Activity Level: Validated methods will be used to measure vector-derived FⅧ activity, including peak and steady state following GS1191-0445 infusion；(Day 4 to Week 52 after infusion)
- Total Consumption of Exogenous FⅧ Infusion;(Weeks 3 to 52 and five years after infusion)
- Annualized Consumption of FⅧ Infusion；(Weeks 3 to 52 and five years after infusion)
- Number of bleeding events requiring exogenous FⅧ infusion: To assess the number of bleeding events requiring exogenous FⅧ infusion after administration;(Weeks 3 to 52 and five years after infusion)
- Number of joint bleeding events: To assess joint bleeding events after administration(Weeks 3 to 52 and five years after infusion)