A Phase 1, First in Man, Multicenter, Open Label, Single Escalating Dose Study of BAY1093884 in Subjects With Severe Hemophilia Types A or B, With or Without Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 32
- 主要终点
- Number of participants (single dose cohors) with adverse events as measure of safety and tolerability
研究概览
简要总结
Investigate the safety, tolerability and pharmacokinetics of BAY1093884 after Intravenous (IV) and subcutaneous (SC) administration of increasing single doses and SC administration of multiple doses.
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
- •Males with severe congenital Hemophilia A or B defined as <1% FVIII or Factor IX (FIX) concentration by measurement at the time of screening or from reliable prior documentation
- •For subjects in Cohorts I-IV, I-SC1 and I-SC2; If history of inhibitors is evident, inhibitor titer of ≥5 Bethesda Units (BU) at screening or prior to screening at any time from medical records.
- •Age: 18 to 65 years of age at screening
- •Body mass index (BMI): 18 to 29.9 kg/m²
排除标准
- •Subjects with known bleeding disorders (such as von Willebrand factor [vWF] deficiency, FXI deficiency, platelet disorders, or known acquired or inherited thrombophilia etc.) other than congenital Hemophilia A or B with or without inhibitors
- •History of angina pectoris or treatment for angina pectoris
- •History of coronary and/or peripheral atherosclerotic disease, congestive heart failure, disseminated intravascular coagulopathy, or stage 2 hypertension defined as systolic blood pressure (SBP) ≥160 mmHg or diastolic blood pressure (DBP) ≥100 mmHg even if controlled
- •History of thrombophlebitis, venous / arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, cerebrovascular accident, ischemic heart disease, transient ischemic attack)
- •Known or suspected hypersensitivity of the immune system, history of anaphylactic reaction, known (clinically relevant) allergies, non-allergic drug reactions, or multiple drug allergies
研究组 & 干预措施
Without inhibitors
Dose escalation steps for participants without inhibitors - intravenous infusion and subcutaneous injection
干预措施: BAY1093884 (Drug)
With inhibitors
Dose escalation steps for participants with inhibitors - intravenous infusion and subcutaneous injection
干预措施: BAY1093884 (Drug)
Without inhibitors_multiple dose
Multiple dose cohort for participants without inhibitors - a single subcutaneous injection once a week for 6 weeks
干预措施: BAY1093884 (Drug)
结局指标
主要结局
Number of participants (single dose cohors) with adverse events as measure of safety and tolerability
时间窗: Up to 56 days
Adverse events including abnormal laboratory findings and local injection site reactions
Plasma levels of anti-BAY1093884 antibodies
时间窗: Pre-dose, Day 14, 21,28, 43 and 56
Plasma concentration of BAY1093884 characterized by Cmax/D
时间窗: Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
Cmax divided by dose
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)
时间窗: Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
AUC from time 0 to the last data point \> LLOQ (lower limit of quantitation)
Plasma concentration of BAY1093884 characterized by AUC(0-tlast)/D
时间窗: Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
AUC(0-last) divided by dose
Plasma concentration of BAY1093884 characterized by Cmax
时间窗: Day 0 [pre-dose (within 1 hour), at the end of infusion or injection (=1hr), 2hrs, 4hrs, 8hrs], Days 1, 3, 5, 7, 14, 21, 28, 43, and 56 (for cohorts 3, 4 and I-SC2, S-2, S-3) after the start of infusion
Maximum observed drug concentration in measured matrix after single dose administration
次要结局
- Number of participants (multiple dose cohort) with adverse events as a measure of safety and tolerability(Up to 77 days)
- Plasma concentration of BAY1093884 characterized by AUC(0-7d/D and AUC(0-tau)/D after multiple dose(Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42)
- Plasma concentration of BAY1093884 characterized by Cmax/D after first dose and last dose (Cmax,md/D)(Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42)
- Tissue factor pathway inhibitor (TFPI) activity(Up to 77 days)
- Plasma levels of anti-BAY1093884 antibodies (multiple dose cohort)(Pre-dose, Day 14, 28, 49 and 77)
- Plasma concentration of BAY1093884 characterized by AUC(0-7d and AUC(0-tau) (multiple dose cohort)(Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42)
- Plasma concentration of BAY1093884 characterized by Cmax after first dose and last dose (Cmax,md)(Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42)
- Accumulation of BAY 1093884 in plasma as defined by ratio for Cmax and AUC (after first and last dose)(Day 0 (prior to start of SC injection) and 8 hrs after start of SC injection, Days 1, 3, 5 and Days 7, and Day 35 (prior to start of SC injection) and 8 hrs after start of SC injection on Day 35; Days 36, 38, 40, 42)