Study of FVIIa Variant BAY86-6150 (B0189) in Subjects With Moderate or Severe Hemophilia Types A or B With or Without Inhibitors

Study Overview
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Brief Summary
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This is the first in humans study of BAY86-6150 (B0189) in non-bleeding subjects with moderate or severe congenital hemophilia A or B with or without inhibitors. This is a randomized, double-blind, placebo-controlled, single-dose, dose escalation study. It is designed to investigate the safety, tolerability, potential immunogenicity, pharmacokinetic and pharmacodynamic profile of BAY86-6150 (B0189) and to determine a dose or range of doses to be examined in subsequent studies.

Official Title
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A Phase I, Randomized, Double-blind, Placebo Controlled, Single Dose Escalation Study of FVIIa Variant BAY86-6150 (B0189) in Subjects With Moderate or Severe Hemophilia Types A or B With or Without Inhibitors

Conditions
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Hemophilia A, Hemophilia B

Intervention / Treatment
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* Drug: BAY Factor VII (BAY86-6150)
* Drug: BAY Factor VII (BAY86-6150)
* Drug: BAY Factor VII (BAY86-6150)
* Drug: BAY Factor VII (BAY86-6150)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of moderate or severe congenital hemophilia A or B with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) Male subjects 18-65 years of age inclusive Able to dismiss factor replacement therapy during the course of the study unless required for the treatment of an acute bleeding episode Written informed consent Willing and able to comply with the requirements of the protocol Have adequate venous access Willing to use an effective method of contraception until Day 30 of their study participation Exclusion Criteria: Received factor replacement therapy or treatment with any other procoagulant therapeutics, or any antifibrinolytic agents, including blood products, at anytime within 5 days prior to administration of investigational medicinal product (IMP) Planned administration of factor replacement therapy or treatment with any other procoagulant therapeutics or any antifibrinolytic agents, including blood products, at anytime during the study period Acute bleeding episode or any ongoing bleeding episode at any time within 7 days prior to administration IMP Clinically relevant coagulation disorder other than congenital hemophilia A or B History of angina or receiving treatment for angina History of coronary atherosclerotic disease, disseminated intravascular coagulopathy, or stage 2 hypertension defined as systolic blood pressure (SBP) >/= 160 mmHg or diastolic blood pressure (DBP) >/= 90 mmHg History of transient ischemic attack, stroke, myocardial infarction, coronary artery disease, congestive heart failure, or thromboembolic event Active infection on day of IMP administration or septicemia at any time within 30 days prior to administration of IMP

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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY Factor VII (6.5 µg/kg) / Placebo<br>n = 4, randomized 3:1; 6.5 µg/kg BAY 86-6150 (B0189):Placebo | Drug: BAY Factor VII (BAY86-6150)<br>* BAY Factor VII (BAY86-6150), 6.5 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>Drug: Placebo<br>* Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>|
| Experimental: BAY Factor VII (20 µg/kg) / Placebo<br>n = 4, randomized 3:1; 20 µg/kg BAY 86-6150 (B0189):Placebo | Drug: BAY Factor VII (BAY86-6150)<br>* BAY Factor VII (BAY86-6150), 20 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>Drug: Placebo<br>* Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>|
| Experimental: BAY Factor VII (50 µg/kg) / Placebo<br>n = 4, randomized 3:1; 50 µg/kg BAY 86-6150 (B0189):Placebo | Drug: BAY Factor VII (BAY86-6150)<br>* BAY Factor VII (BAY86-6150), 50 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>Drug: Placebo<br>* Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>|
| Experimental: BAY Factor VII (90 µg/kg) / Placebo<br>n = 4, randomized 3:1; 90 µg/kg BAY 86-6150 (B0189):Placebo | Drug: BAY Factor VII (BAY86-6150)<br>* BAY Factor VII (BAY86-6150), 90 µg/kg body weight, will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>Drug: Placebo<br>* Placebo will be administered as a slow intravenous (i.v.) administration over a period of 2-5 minutes (min) on Study Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability |  | Up to Day 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessment, based on plasma concentration of BAY86-6150 |  | 9 time points from pre-dosing on Day 1 up to 48 hours post-dosing | 
| Pharmacodynamic assessment, based on plasma hemostasis marker level |  | 9 time points from pre-dosing on Day 1 up to 48 hours post-dosing | 
| Immunogenicity assessment, based on anti-BAY86-6150 binding antibody levels |  | 3 time points from pre-dosing on Day 1 up to Day 50 |