Phase 3, Prospective, Multi-center, Open Label Study to Investigate Safety, Immunogenicity and Hemostatic Efficacy of PEGylated Factor VIII (BAX 855) in Previously Untreated Patients (PUPs) < 6 Years With Severe Hemophilia A (FVIII < 1%)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 89
- 主要终点
- Number of Participants With FVIII Inhibitor Development
研究概览
简要总结
This study is for young children with severe hemophilia A who have previously not been treated with BAX855 or other FVIII concentrates.
The main aim of the study is to check for side effects from treatment with BAX855. This includes the buildup of antibodies against FVIII which may stop BAX855 from working properly. Another aim is to learn how well BAX855 controls bleeding.
In this study, the children can receive BAX855 either as preventative treatment (prophylaxis), or as needed to treat bleeding (on-demand).
In case a participant develops antibodies, treatment will be provided as part of the study.
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
- — 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
All Participants
Previously Untreated Patients (PUPs) < 6 years of age with severe hemophilia A (FVIII < 1%) and < 3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion were enrolled in a single arm group.
Part A (Main Study): Participants age <3 years - who had not experienced two joint bleeds received on-demand treatment of 10-80 international units per kilogram (IU/kg) intravenously (IV) depending on the severity of the bleeding episode; and - who experienced maximum of two joint bleeds received prophylaxis treatment with dose of 25-80 IU/kg of BAX 855 IV (based on investigator discretion) once weekly for up to 100 EDs.
Part B (Immune tolerance induction [ITI] Portion): Participants who met the pre-defined Part B treatment criteria entered Part B of the study for ITI. Participants either received prophylaxis treatment of BAX 855 low dose 50 IU/kg IV, three times a week or high dose 100-200 IU/kg IV, daily at discretion of the investigator according to the institution's standard of care.
干预措施: PEGylated Recombinant Factor VIII (Biological)
All Participants
Previously Untreated Patients (PUPs) < 6 years of age with severe hemophilia A (FVIII < 1%) and < 3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion were enrolled in a single arm group.
Part A (Main Study): Participants age <3 years - who had not experienced two joint bleeds received on-demand treatment of 10-80 international units per kilogram (IU/kg) intravenously (IV) depending on the severity of the bleeding episode; and - who experienced maximum of two joint bleeds received prophylaxis treatment with dose of 25-80 IU/kg of BAX 855 IV (based on investigator discretion) once weekly for up to 100 EDs.
Part B (Immune tolerance induction [ITI] Portion): Participants who met the pre-defined Part B treatment criteria entered Part B of the study for ITI. Participants either received prophylaxis treatment of BAX 855 low dose 50 IU/kg IV, three times a week or high dose 100-200 IU/kg IV, daily at discretion of the investigator according to the institution's standard of care.
干预措施: ITI (Biological)
结局指标
主要结局
Number of Participants With FVIII Inhibitor Development
时间窗: Throughout Part A of the study, approximately 5 years
Number of participants who developed an inhibitor (at any time) confirmed by a central laboratory based on a second repeat blood sample draw within 2 weeks of site notification of an inhibitor and all participants who had not developed an inhibitor and had greater than or equal to (\>=) 100 EDs when the sample for the last valid inhibitor test was drawn.
Number of Participants With Success of Immune Tolerance Induction (ITI)
时间窗: Up to 33 months in Part B of the study
Success is defined as 1) a persistently negative inhibitor titer less than (\<) 0.6 Bethesda unit (BU), 2) FVIII IR \>=66% of the baseline value following a wash-out period of 84-96 hours, and 3) a FVIII half-life of \>=6 hours.
次要结局
- Number of Participants With Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies(Throughout Part A of the study, approximately 5 years)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Throughout Part A and Part B of the study, approximately 9 years)
- Number of Participants With At Least One Clinically Significant Changes in Vital Signs(Throughout Part A and Part B of the study, approximately 9 years)
- Number of Participants With At Least One Clinically Significant Changes in Clinical Laboratory Parameters(Throughout Part A and Part B of the study, approximately 9 years)
- Annualized Bleeding Rate (ABR) for Prophylactic and On-demand Treatment and Immune Tolerance Induction (ITI)(Throughout Part A and Part B of the study, approximately 9 years)
- Bleeding Episodes Categorized by Number of BAX 855 Infusions Required for Treatment(Throughout Part A of the study, approximately 5 years)
- Number of Bleeds by Overall Hemostatic Efficacy Rating at 24 Hours After Initiation of Treatment(At 24 hours after study drug administration during Part A of the study)
- Number of Bleeds by Overall Hemostatic Efficacy Rating at Bleed Resolution(From start of study treatment up to bleed resolution throughout Part A of the study (up to approximately 5 years))
- Weight-adjusted Consumption of BAX 855: Average Prophylactic Dose(Throughout Part A of the study, approximately 5 years)
- Weight-adjusted Consumption of BAX 855: Average Number of Prophylactic Infusions(Throughout Part A and Part B of the study, approximately 9 years)
- Weight-adjusted Consumption of BAX 855: Average Dose(Throughout Part A of the study, approximately 5 years)
- Number of Participants by Hemostatic Efficacy Rating in Case of Surgery(Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first))
- Blood Loss Per Participant in Case of Surgery(Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first))
- Incremental Recovery (IR) of BAX 855(Baseline up to Study Completion (Up to 5 years in Part A and up to 3.5 years in Part B))
- Half-life (T1/2) of BAX 855(Pre-infusion, Post-infusion: 15-30 minutes and 24-48 hours at Baseline)
- Immune Tolerance Induction (ITI) - Number of Participants With Partial Success and Failure of ITI(Up to 33 months in Part B of the study)
- Immune Tolerance Induction (ITI) - Number of Participants With At Least One Catheter-related Complication(Up to 33 months in Part B of the study)
- Immune Tolerance Induction (ITI) - Number of Participants With Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies(Up to 33 months in Part B of the study)