An Open-label Phase 1 Trial to Evaluate the Pharmacokinetics and Safety Profile of BAY94-9027 Following Single and Multiple Dose Administration in Two Cohorts of Previously Treated Male Subjects With Severe Hemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Safety as assessed by measuring immunogenicity
研究概览
简要总结
The purpose of this study is to describe the pharmacokinetics (PK) of BAY94-9027(the test drug). Pharmacokinetics means that we will measure how well the study drug corrects the factor VIII levels in your blood and how long it takes for the levels to fall back to your baseline level. The study is also designed to determine if the pharmacokinetics of BAY94-9027 change following repeat dosing over 8 weeks, determine if BAY94-9027 is safe, tolerable, and effective for the treatment of severe hemophilia A and define the appropriate dose of BAY94-9027. Two doses of BAY94-9027 will be studied.
The first 8 subjects enrolled in the study (cohort 1) will receive a low dose (25 IU/kg) and will be treated 2 days a week for 8 weeks (total of 16 doses). The second 8 subjects (cohort 2) will receive a higher dose and will be treated 1 day a week for 8 weeks (total 8 doses). All subjects will receive a single dose of rFVIII (Bayer Kogenate FS) to determine the PK by measuring blood levels for 2 days before they start the study drug BAY94-9027. Factor VIII blood levels for BAY94-9027 will be measured for 7 days after the first and last dose to see describe the PK. Safety & tolerability assessment include vital signs, coagulation and hematological parameter, clinical chemistry, measurement of FVIII inhibitor and polyethylene glycol (PEG) antibodies will be done during the course of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male subjects with severe hemophilia A (documented plasma baseline Factor VIII level <1 %)
- •>/= 18 but </= 65 years of age
- •Previously treated with Factor VIII concentrate(s) for a minimum of 150 exposure days (as supported by the subject's medical history)
- •Immunocompetent with a CD4+ lymphocyte count > 400/mm³
- •Signed informed consent from subject
排除标准
- •Documented history of inhibitor to Factor VIII with a titer >/= 0.6 BU (Biological Unit), by the Nijmegen modified assay. However, subjects with a maximum historical titer of </= 1.0 BU with the classical Bethesda assay on a single measurement but with at least 3 subsequent successive negative results (< 0.6 BU) thereafter are eligible.
- •Unable to stop Factor VIII treatment to complete a minimum 72 hour washout
- •Current evidence of inhibitor to Factor VIII with a titer >/= 0.6 BU, measured at the time of screening
- •Abnormal renal function (serum creatinine > 1.5 times the upper limit of the normal range)
- •Total bilirubin > 1.5 times the upper limit of the normal range
- •Active hepatic disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 2 times the upper limit of the normal range)
- •Any concomitant coagulation disorder other than hemophilia A (including lupus anticoagulant)
- •Platelet count < 100,000/mm³
- •Within the last 3 months prior to study entry or during the study will be treated with an immunomodulating drug other than anti-retroviral chemotherapy (e.g., a interferon, steroids, rituximab, etc)
- •Any subject who requires major surgery during study period. Minor procedures may be approved if discussed in advance with the medical expert.
研究组 & 干预措施
Arm 1
干预措施: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222) (Biological)
Arm 2
干预措施: BAY94-9027 + Recombinant Factor VIII (Kogenate FS, BAY14-2222)) (Biological)
结局指标
主要结局
Safety as assessed by measuring immunogenicity
时间窗: Up to 8 weeks
Antibodies to FVIII, polyethylene glycol (PEG) and BAY94-9027
Adverse events collection
时间窗: Up to 8 weeks
Area under the plasma concentration vs time curve from time 0 to the last data point (AUC0-tlast)
时间窗: Up to 8 weeks
Area under the plasma concentration vs time curve from zero to infinity after single (first) dose (AUC0-inf)
时间窗: Up to 8 weeks
Maximum drug concentration in plasma (Cmax)
时间窗: Up to 8 weeks
Half-life associated with the terminal slope (t1/2)
时间窗: Up to 8 weeks
Time to reach maximum drug concentration in plasma after single (first) dose (Tmax)
时间窗: Up to 8 weeks
Mean residence time (MRT)
时间窗: Up to 8 weeks
Total body clearance (CL)
时间窗: Up to 8 weeks
Total body clearance of drug from plasma (volume/time) or (volume/time/body weight) or ((volume/time)\*(1.73/body surface area)) calculated after intravenous administration
Apparent volume of distribution at steady state (Vss)
时间窗: Up to 8 weeks
Based on the chromogenic, one-stage and PEG capture assays
Incremental recovery of FVIII
时间窗: Up to 8 weeks
Recovery was assessed using two different assays (chromogenic and one-stage assay)
次要结局
未报告次要终点