Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 21
- 主要终点
- Annualized Infusion Rate
研究概览
简要总结
SPK-8016 is in development for the treatment of patients with inhibitors to FVIII. This Phase 1/2, open-label, non-randomized, dose-finding study to evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with severe hemophilia A and no measurable inhibitor against FVIII.
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
- •Be male and ≥18 years of age;
- •Have clinically severe hemophilia A, defined as:
- •<1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR
- •1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year (in the last 52 weeks prior to screening); OR
- •1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis;
- •Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates
- •Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration
- •Have no measurable inhibitor against FVIII as assessed by central laboratory, have no confirmed history of clinically significant FVIII inhibitor, and no clinical signs or symptoms of decreased response to FVIII administration (Note: family history of inhibitors will not exclude study participation)
- •Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator.
排除标准
- •Have active hepatitis B or C
- •Have significant underlying liver disease.
- •Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm
- •Participants who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load, and are on an antiretroviral drug regimen are eligible to enroll
- •Have detectable antibodies reactive with AAV-Spark capsid
- •Have history of chronic infection or other chronic disease
- •Have been dosed in a previous gene therapy research trial within the last 52 weeks or with an investigational drug within the last 12 weeks
- •Any concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) or other condition that, in the opinion of the Investigator and/or Sponsor, makes the subject unsuitable for participation in the study;
- •Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.
结局指标
主要结局
Annualized Infusion Rate
时间窗: From 28 days post vector administration up to week 52
Number of Participants With Hepatic Transaminase Elevation Requiring Immunosuppression.
时间窗: Up to week 52
Number of Participants With Adverse Events (AEs)
时间窗: Up to week 52
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Bleeding Events (Spontaneous and Traumatic) Since 28 Day Post Vector Administration
时间窗: From 28 days post vector administration up to week 52
Peak FVIII Activity Levels Assessed by Coagulation Clotting Assays
时间窗: Up to week 52
Steady-state FVIII Activity Levels Assessed by Coagulation Clotting Assays
时间窗: Up to week 52
次要结局
- Time to Achieve Steady-state FVIII Activity Levels(Up to week 52)
- Number of Participants With Immune Responses to AAV Capsid Protein and BDD-hFVIII Transgene(Up to week 52)
- Number of Participants With Vector-shedding of SPK-8016 in Bodily Fluids(Up to week 52)