A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 49
- 主要终点
- Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.
研究概览
简要总结
This Phase III clinical study will assess the impact of BMN 270 (compared to FVIII prophylaxis) on the number of bleeding episodes irrespective of exogenous FVIII replacement treatment in the efficacy evaluation period (EEP) (from Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). The study will also assess the impact of BMN 270 (compared to FVIII prophylaxis) on: the number of bleeding episodes requiring exogenous FVIII treatment in "Post FVIII Prophylaxis to Last Visit", FVIII activity as measured by chromogenic sustrate assay at Week 104 following intravenous infusion of BMN 270, usage of exogenous FVIII replacement therapy in "Post FVIII Prophylaxis to Last Visit", health-related quality of life patient-reported outcomes at week 104 following intravenous infusion of BMN 270. The study will also evaluate the safety of the BMN 270.
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 of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history, at the time of signing the informed consent.
- •Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.
- •Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
- •No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months.
排除标准
- •Detectable pre-existing antibodies to the adeno-associated virus 5 (AAV5) capsid.
- •Any evidence of active infection or any immunosuppressive disorder, except for HIV infection
- •Any evidence of active infection or any immunosuppressive disorder, including HIV infection (effective as of Protocol Amendment 3)
- •Significant liver dysfunction.
- •Prior liver biopsy showing significant fibrosis.
- •Evidence of any bleeding disorder not related to hemophilia A.
- •Platelet count of < 100 x 10^9/L.
- •Creatinine ≥ 1.5 mg/dL.
- •Liver cirrhosis of any etiology as assessed by liver ultrasound.
- •Chronic or active hepatitis B.
- •Active Hepatitis C.
- •Active malignancy, except non-melanoma skin cancer.
- •History of hepatic malignancy.
- •History of arterial or venous thromboembolic events.
- •Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.
研究组 & 干预措施
valoctocogene roxaparvovec Open Label
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
干预措施: valoctocogene roxaparvovec (Biological)
结局指标
主要结局
Change From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.
时间窗: Baseline to efficacy evaluation period (EEP)
All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period \* 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. EEP: From Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit").
次要结局
- Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP.(Baseline to EEP)
- Change From Baseline in Haemo-QoL-A Quality of Life: Role Functioning Domain Score, at Week 104(Baseline to Week 104)
- Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104(Baseline to Week 104)
- Change From Baseline in FVIII Activity at Week 104(Baseline to Week 104)
- Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104(Baseline to Week 104)
- Change From Baseline in Annualized FVIII Utilization in EEP.(Baseline to EEP)
- Change From Baseline in Haemo-QoL-A Quality of Life: Consequences of Bleeding Domain Score, at Week 104(Baseline to Week 104)