Gene-transfer, Open-label, Dose-escalation Study of SPK-8011 [Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene] in Individuals With Hemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 31
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This clinical research study is being conducted by Spark Therapeutics, Inc. to determine the safety and efficacy of the factor VIII gene transfer treatment with SPK-8011 in individuals with hemophilia A.
详细描述
Hemophilia A is a condition in which blood is unable to clot effectively. It is caused by a mutation or deletion in the gene that is responsible for producing blood-clotting factor VIII protein. Individuals with hemophilia A suffer from repeated bleeding episodes, often into the joints, which can cause chronic joint disease and sometime results in death due to the inability of the blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current standard of care includes the use of factor-based therapies which are given either as prophylaxis or to treat bleeding, as well as new non-factor prophylaxis therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Males age 18 years or older
- •Confirmed diagnosis of hemophilia A as evidenced by their medical history with baseline FVIII activity levels <=2%
- •Have received >150 exposure days (EDs) to FVIII concentrates or cryoprecipitate
- •Have no prior history of allergic reaction to any FVIII product
- •Have no measurable inhibitor against FVIII as assessed by the central laboratory and have no prior history of inhibitors to FVIII protein and no clinical signs or symptoms of decreased response to FVIII administration
- •Agree to use reliable barrier contraception
排除标准
- •Evidence of active hepatitis B or C
- •Currently on antiviral therapy for hepatitis B or C
- •Have significant underlying liver disease
- •Have serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 and who are on an antiretroviral drug regimen (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
- •Have detectable antibodies reactive with AAV-Spark200 capsid
- •Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational product within the last 12 weeks
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From date of first dose to Week 52/End of Study (EOS) Visit
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (SAEs) were defined as adverse events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, are a congenital anomaly or birth defect, or are an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE is defined as an AE with an onset date on or following SPK-8011 administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants Who Received Corticosteroids for Presumed Immune Response
时间窗: Up to Week 52/EOS Visit
Peak Factor VIII (FVIII) Activity Levels Assessed by One-Stage Coagulation Assay (OSA)
时间窗: Up to Week 52/EOS visit
Median peak FVIII activity up to Week 52
Nominal FVIII Level by OSA at Week 52/EOS
时间窗: Up to Week 52/EOS Visit
Steady-state FVIII activity measured by median FVIII levels at week 52 by OSA.
Spontaneous Bleeds Annualized Bleeding Rate
时间窗: Week 5 up to Week 52/EOS Visit
Total Annualized FVIII Infusion Rate
时间窗: Week 5 up to Week 52/EOS Visit
次要结局
- Incidence of Immune Response to the BDD-hFVIII Transgene(Up to Week 52/EOS Visit)
- Time to Achieve Peak FVIII Activity Level(Up to Week 52/EOS Visit)
- Number of Participants With Vector-shedding Confirmed Below Quantifiable Limits (BQL) of SPK-8011-101 in Bodily Fluids(Up to Week 52/EOS Visit)