A Phase III Open Label, Multicenter, Extension Study to Assess the Safety and Efficacy of Recombinant Coagulation Factor VIII (rVIII-SingleChain, CSL627) in Subjects With Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 246
- 试验地点
- 128
- 主要终点
- Percent Treatment Success for Major Bleeding Episodes in PUPs
研究概览
简要总结
This multicenter, open-label, phase 3 extension study will investigate the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in at least 200 previously treated patients (PTPs) with severe congenital hemophilia A and previous exposure to FVIII products who achieve at least 100 exposure days (EDs) to rVIII-SingleChain in this study, as well as in previously untreated patients (PUPs) with no previous exposure to any FVIII product who achieve at least 50 EDs to rVIII-SingleChain in this study. A substudy (open to both PTPs and PUPs) will investigate the use of rVIII-SingleChain in surgery. A substudy (open to PUPs who develop an inhibitor to rVIII-SingleChain) will investigate the use of rVIII-SingleChain in immune tolerance induction (ITI) therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%) and who participated in a previous CSL-sponsored clinical study with rVIII-SingleChain.
- •Males 0 to <65 years age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%), who have at least 50 EDs to any FVIII product, and who are not currently enrolled in a CSL-sponsored clinical study with rVIII-SingleChain.
- •Males 0 to <18 years of who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%)
- •No prior exposure to any Factor VIII product (with the exception of short-term use of blood products).
- •ITI substudy:
- •PUPs who have developed a confirmed inhibitor to rVIII-SingleChain in the main study.
排除标准
- •Known or suspected hypersensitivity to rVIII-SingleChain or to any excipients of rVIII-SingleChain or Chinese hamster ovary (CHO) proteins.
- •Currently receiving a therapy not permitted during the study.
- •Serum creatinine > 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase > 5 x upper limit of normal at Screening (if specified)
- •Any first-order family (eg, siblings) history of FVIII inhibitors
- •For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors
结局指标
主要结局
Percent Treatment Success for Major Bleeding Episodes in PUPs
时间窗: Up to 5 years
Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.
Annualized Spontaneous Bleeding Rate in PUPs
时间窗: Up to 5 years
The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.
Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627
时间窗: At the closest visit after 100 EDs (up to 5 years).
Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627
时间窗: At the closest visit after 50 EDs (up to 5 years).
High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.
次要结局
- Mean On-demand Dose Administered of CSL627(Up to 5 years)
- Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery(From the start of surgery through the post-operative recovery (generally up to 14 days after surgery))
- Mean Prophylaxis Dose Administered of CSL627(Up to 5 years)
- Annualized Bleeding Rate in PTPs and PUPs(Up to 5 years)
- Total Amount of CSL627 Administered During Surgery Period in PUPs(Day of surgery up to 336 hours post-surgery)
- Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs(Up to 5 years)
- Percentage of PTPs and PUPs Developing Antibodies Against CSL627(PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).)
- Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins(PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).)
- Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs(Up to 5 years)
- Mean Number of On-demand Infusions of CSL627(Up to 5 years)
- Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627(At the closest visit after 10 and after 50 EDs (up to 5 years))
- Percentage of Bleeding Episodes Treated Successfully in PTPs(Up to 5 years)
- Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627(Up to 6 hours after first infusion)
- Mean Total Amount of CSL627 Administered During Surgery Period in PTPs(Day of surgery up to 336 hours post-surgery)
- Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627(At the closest visit after 10 EDs (up to 5 years))
- Incidence of Total Inhibitor Formation to FVIII in PUPs(Up to 5 years)
- Percent Treatment Success for Non-major Bleeding Episodes in PUPs(Up to 5 years)
- Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values(Up to 5 years)