A Study to Assess Pharmacokinetics and Pharmacodynamics Following Administration of BAY1093884 in Patients With Severe Hemophilia

Study Overview
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Brief Summary
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The primary objective of this study is to assess the pharmacokinetics in patients with severe hemophilia. The secondary objective is to assess the pharmacodynamics of BAY1093884 based on tissue factor pathway inhibitor activity

Official Title
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A Phase 1 Study to Assess Pharmacokinetics and Pharmacodynamics Following Administration of BAY1093884 in Patients With Severe Hemophilia

Conditions
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Hemophilia A; Hemophilia B

Intervention / Treatment
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* Drug: BAY1093884
* Drug: BAY1093884


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males with severe congenital hemophilia A or B defined as <1% FVIII or <2% FIX concentration by measurement at the time of screening or from reliable prior documentation (e.g., measurement in other clinical Bayer trials, or diagnostic genetic testing) Male with any inhibitor titer at screening or prior to screening at any time from medical records. Subjects may be receiving a bypassing agent (rFVIIa; NovoSeven and/or aPCC; FEIBA) for treatment. Age: 18 to 65 years at screening BMI: 18 to 29.9 kg/m2 Exclusion Criteria: 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 severe allergies, non-allergic drug reactions, or multiple drug allergies Subjects with inhibitors treated with FEIBA, who are not willing to accept rFVIIa (NovoSeven) for the treatment of any bleeds occurring either between screening and dosing or after study drug administration, and until the end of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1093884 in subjects with Hemophilia<br>Single dose of BAY1093884 over 30 minutes administered in subjects with severe congenital Hemophilia A or B, with inhibitors or without inhibitors | Drug: BAY1093884<br>* 0.3 mg/kg given intravenously<br>Drug: BAY1093884<br>* 1 mg/kg given intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-tlast) of BAY1093884 in plasma | Area under the concentration vs. time curve from time 0 to the last data point > LLOQ | Up to 15 days after drug administration | 
| AUC(0-tlast)/D of BAY1093884 in plasma | AUC(0-tlast) divided by dose | Up to 15 days after drug administration | 
| Cmax of BAY1093884 in plasma | Maximum observed drug concentration in measured matrix after single dose administration | Up to 15 days after drug administration | 
| Cmax/D of BAY1093884 in plasma | Cmax divided by dose | Up to 15 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue factor plasma inhibitor activity: effect of BAY1093884 to inhibit the anticoagulatory activity of plasma TFPI as assessed by a chromogenic assay |  | Up to 15 days after drug administration |