A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events
研究概览
简要总结
This study is being conducted by BioMarin Pharmaceutical Inc. as an open label, dose escalation study in order to determine the safety and efficacy of valoctocogene roxaparvovec (an Adenovirus-Associated Virus based gene therapy vector in participants with severe haemophilia A.
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
- •Males 18 years or older with established severe Haemophilia A (endogenous FVIII level ≤1 IU/dL) as evidenced by their medical history.
- •Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
- •Greater than or equal to 12 bleeding episodes for patients on on-demand FVIII replacement therapy over the previous 12 months. Does not apply to patients on prophylaxis
- •No history of inhibitor, and results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) 2 consecutive occasions at least one week apart within the past 12 months
- •Sexually active patients must be willing to use an acceptable method of contraception.
排除标准
- •Detectable pre-existing immunity to the AAV5 capsid as measured by adeno-associated virus 5 (AAV5) transduction inhibition (TI) or AAV5 total antibodies
- •Any evidence of immunosuppressive disorder or active chronic infection including hepatis B, hepatitis C, HIV
- •Significant liver dysfunction as defined by abnormal elevation ofliver function tests, or for patients who have undergone liver imaging or biopsy and found to have evidence of grade 3 or higher fibrosis
- •Evidence of any bleeding disorder not related to haemophilia A
- •Treatment with any investigational product within 30 days prior to the end of the screening period, or any previous exposure to any gene transfer therapy
- •Any disease or condition that per the physician's discretion would prevent the patient from fully complying with the requirements of the study including possible corticosteroid treatment outlined in the protocol. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion.
研究组 & 干预措施
valoctocogene roxaparvovec
Single administration of valoctocogene roxaparvovec at escalating doses.
干预措施: valoctocogene roxaparvovec (Biological)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events
时间窗: Approximately up to 7 years after dosing
Adverse events (AEs) with onset or worsening after the investigational product were included. Participants with more than one AE of the same category were counted only once for that category. Serious adverse event (SAE)
Number of Participant With Median FVIII Activity Levels >= 5 IU/dL Using Chromogenic Substrate Assay (CSA)
时间窗: Week 13-16 post-BMN 270 infusion
Responder/Non responder status, where a responder was defined as a participant with median FVIII activity of \>= 5 IU/dL during Week 13-16 post-BMN 270 infusion
Median FVIII Activity as Measured by Chromogenic Substrate Assay During Week 13-16 Post-BMN 270 Infusion
时间窗: Week 13-16 post-BMN 270 infusion
Values for FVIII activity were excluded from analysis if obtained within 72 hours since the last infusion of exogenous FVIII replacement therapy FVIII activity levels below the Lower limit of quantitation (LLOQ) will be imputed with 0 IU/dL Q1: 25% Percentile; Q3: 75% Percentile
次要结局
- Annualized Factor VIII Utilization During Week 5 and Beyond(Week 5 and Beyond (Approximately 7 years post Infusion))
- Annualized Factor VIII Infusion Rate During Week 5 and Beyond(Week 5 and Beyond (Approximately 7 years post Infusion))
- Annualized Bleeding Rate Requiring Exogenous Factor VIII Replacement Treatment During Week 5 and Beyond(Week 5 and Beyond (Approximately 7 years post Infusion))