Phase III, Open-label, Single-dose, Multi-center, Multinational Trial Investigating a Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 67
- 试验地点
- 33
- 主要终点
- Annualized Bleeding Rate (ABR) for All Bleeding Episodes
研究概览
简要总结
This is an open-label, single-dose, multi-center, multinational trial to demonstrate the efficacy of AMT-061 and to further describe its safety profile.
The study drug is identified as AAV5-hFIXco-Padua (AMT- 061). AMT-061 is a recombinant adeno-associated viral vector of serotype 5 (AAV5) containing the Padua variant of a codon-optimized human FIX complementary deoxyribonucleic acid (cDNA) under the control of a liver-specific promoter. The pharmaceutical form of AMT-061 is a solution for intravenous infusion administered at a dose of 2 x 10^13 gc/kg.
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
- •Age ≥18 years
- •Subjects with congenital hemophilia B, classified as severe or moderately severe, and are currently on factor IX prophylaxis
- •>150 previous exposure days of treatment with factor IX protein
排除标准
- •History of factor IX inhibitors
- •Positive factor IX inhibitor test at screening
- •Select screening laboratory value >2 times upper limit of normal
- •Positive human immunodeficiency virus (HIV) test at screening, not controlled with anti-viral therapy
- •Active infection with hepatitis B or C virus at screening
- •History of Hepatitis B or C exposure, currently controlled by antiviral therapy at the end of the lead-in phase
- •Previous gene therapy treatment
- •Receipt of an experimental agent within 60 days prior to screening
- •Current participation or anticipated participation within one year after study drug administration in this trial in any other interventional clinical trial involving drugs or devices
研究组 & 干预措施
AMT-061
Single infusion of AMT-061
Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After study drug administration (post study drug), subjects will be monitored for tolerance to the study drug and detection of potential immediate AEs at the clinical trial site for a few hours after dosing.
干预措施: AAV5-hFIXco-Padua (Genetic)
FIX replacement (Lead-in Period)
During the lead-in phase, which lasted for a minimum of 26 weeks (i.e., ≥6 months), subjects recorded their use of FIX replacement therapy and bleeding episodes in their dedicated e-diary.
干预措施: Factor IX (FIX) (Biological)
结局指标
主要结局
Annualized Bleeding Rate (ABR) for All Bleeding Episodes
时间窗: Lead-in period and months 7-18 post-treatment of AMT-061
ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
次要结局
- Mean FIX Activity (%) in Subjects With Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing(Baseline and 6,12, and 18 months after AMT-061 dosing)
- Mean FIX Activity (%) in Subjects Without Pre-Existing Neutralizing Antibodies to AAV5 After AMT-061 Dosing(Baseline and 6,12, and 18 months after AMT-061 dosing)
- Annualized Exogenous Factor IX Consumption(Lead-in period and months 0-6, 7-12, and 13-18 after AMT-061 dosing)
- Percentage of Subjects With Trough FIX Activity <12% of Normal(Lead-in and 3, 12, and 18 months after AMT-061 dosing)
- Number of Spontaneous Bleeding Episodes(Lead-in period and months 7-18 after AMT-061 dosing)
- Percent of Subjects Who Discontinued FIX Prophylaxis and Remained Free of Routine FIX Prophylaxis After AMT-061 Dosing(Months 7-18 after AMT-061 dosing)
- Factor IX Activity Levels After AMT-061 Dosing(Baseline and 6,12, and 18 months after AMT-061 dosing)
- Adjusted Annualized Infusion Rate of FIX Replacement Therapy(Lead-in period and months 7-18 after AMT-061 dosing)
- Number of Joint Bleeding Episodes(Lead-in period and months 7-18 after AMT-061 dosing)
- ABR for FIX-treated Bleeding Episodes(Lead-in and Months 7-18 after AMT-061 dosing)
- Number of New Target Joints and the Number of New Target Joints Resolved.(Up to 18 months after AT-061 dosing)
- International Physical Activity Questionnaire (iPAQ) Overall Score(Lead-in period and up to 12 months after AT-01 dosing)
- Percent of Participants With Zero Bleeding Episodes During the 52 Weeks Following Stable FIX Expression (6 to 18 Months) After AMT-061 Dosing(Lead-in period and months 7-18 post-treatment of AMT-061)
- Number of Adverse Events(5 years)
- EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score(Lead-in period and up to 12 months after AMT-061 dosing)